Systems and methods for inspecting a microfluidic rotor device

ABSTRACT

Described herein are various embodiments directed to rotor devices, systems, and kits. Embodiments of rotors disclosed herein may be used to characterize one or more analytes of a fluid. A method may include aligning an apparatus to an imaging device. The apparatus may include a set of wells defined by a first layer coupled to a second layer. The first layer may be substantially transparent to infrared radiation. The second layer may define a channel. The second layer may be substantially absorbent to the infrared radiation. The apparatus may further include a third layer coupled to the second layer and define an opening configured to receive a fluid. The third layer may be substantially transparent to the infrared radiation. A set of images of the apparatus may be generated using the imaging device. Bonding information may be generated based on the set of images.

CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional PatentApplication No. 62/722,450, filed Aug. 24, 2018, which is expresslyincorporated herein by reference in its entirety.

BACKGROUND

Analysis of fluids from a subject may be used as a diagnostic tool fordisease and to monitor subject health. For example, analysis of asubject's blood sample may be used to diagnose a disease and/or used toquantify one or more analytes within the sample. Some systems opticallyanalyze a blood sample applied to a rotor where the rotor includes a setof reagents disposed within a set of cuvettes. Inspection of one or morerotor welds, sample, and reagents within conventional rotors may bedifficult and/or time consuming. Moreover, a rotor undergoingcentrifugation may generate undesirable, high-decibel noise due to theunbalanced nature of asymmetric fluid flow within the rotor. Therefore,additional devices, systems, and methods for performing fluid analysismay be desirable.

SUMMARY

In general, a method includes aligning an apparatus to an imagingdevice. The apparatus may include a set of wells defined by a firstlayer coupled to a second layer. The first layer may be substantiallytransparent to infrared radiation. The second layer may define achannel. The second layer may be substantially absorbent to the infraredradiation. The apparatus may further include a third layer coupled tothe second layer and define an opening configured to receive a fluid.The third layer may be substantially transparent to the infraredradiation. A set of images of the apparatus may be generated using theimaging device. Bonding information may be generated based on the set ofimages. The bonding information may include a set of edges and gapsformed between the second layer and the third layer. A weld quality ofthe apparatus may be classified using the bonding information.

In some embodiments, the set of images may include one or more of a planview of the apparatus, a bottom view of the apparatus, a side view ofthe apparatus, and a skew view of the apparatus. In some embodiments,the set of images generated may further include illuminating theapparatus. In some of these embodiments, illuminating the apparatus mayinclude employing diffuse axial illumination. In some embodiments,classifying the apparatus further includes identifying one or more of anumber, size, shape, and location of a set of defects in the apparatus.In some of these embodiments, classifying the apparatus may include aset of rotor classifications including one or more of rejected,acceptable, limited release, and requiring secondary inspection. In someembodiments, aligning the apparatus may include orienting the imagingdevice substantially parallel to the apparatus. In some embodiments,aligning the apparatus may include orienting the imaging devicesubstantially perpendicular to the apparatus.

In some embodiments, a method may include aligning the apparatus to animaging device. The apparatus may include a set of wells defined by afirst layer coupled to a second layer. The first layer may besubstantially transparent to infrared radiation. The second layer maydefine a channel. The second layer may be substantially absorbent to theinfrared radiation. The apparatus may further include a third layercoupled to the second layer and define an opening configured to receivea fluid. The third layer may be substantially transparent to theinfrared radiation. One or more wells of the set of wells may include areagent. A set of reagent images may be generated using the imagingdevice. Reagent information may be generated from the reagent images.The reagent information may include a shape and size of the reagent. Areagent quality may be classified using the reagent information.

In some embodiments, the set of reagent images may include one or moreof a plan view of the reagent, a bottom view of the reagent, and a sideview of the reagent. In some embodiments, the reagent may be illuminatedwhen generating the reagent images. In some embodiments, the reagent maybe illuminated by employing diffuse axial illumination. In someembodiments, classifying the reagent quality includes identifying one ormore of a number, size, shape, color, and location of the reagent in theapparatus. In some of these embodiments, classifying the reagent qualityincludes a set of rotor classifications including one or more ofrejected, acceptable, limited release, and requiring secondaryinspection. In some embodiments, aligning the apparatus includesorienting the imaging device substantially parallel to the apparatus. Insome embodiments, aligning the apparatus includes orienting the imagingdevice substantially perpendicular to the apparatus. The reagent may bea lyophilized reagent.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is an illustrative plan view of a rotor, according toembodiments.

FIG. 1B is an illustrative bottom view of the rotor depicted in FIG. 1A.

FIG. 2A is an illustrative exploded view of a rotor assembly, accordingto other embodiments.

FIG. 2B is another illustrative exploded view of the rotor assemblydepicted in FIG. 2A.

FIG. 2C is an illustrative assembled perspective view of the rotorassembly depicted in FIG. 2A.

FIG. 3A is a cross-sectional side view of a rotor, according to otherembodiments.

FIG. 3B is a detailed cross-sectional side view of a well of the rotordepicted in FIG. 3A.

FIG. 4A is a detailed plan view of a set of wells and a set ofreflectors of a rotor, according to embodiments.

FIG. 4B is a detailed plan view of an inlet and channel of a rotor,according to embodiments.

FIG. 4C is a cross-sectional side view of the reflector depicted in FIG.4A.

FIG. 5A is a detailed plan view of an arcuate cavity of a rotor,according to embodiments.

FIG. 5B is a detailed cross-sectional side view of the arcuate cavitydepicted in FIG. 5A.

FIG. 6 is a detailed plan view of a channel of a rotor, according toembodiments.

FIG. 7A is an illustrative exploded view of a rotor assembly, accordingto other embodiments.

FIG. 7B is a detailed perspective view of a layer of the rotor assemblydepicted in FIG. 7A.

FIG. 8A is a block diagram of a fluid analysis system, according toother embodiments.

FIG. 8B is a block diagram of a control system of the fluid analysissystem depicted in FIG. 8A.

FIG. 9 is an illustrative flowchart of a method of using a rotor,according to embodiments.

FIG. 10A is an illustrative flowchart of a method of manufacturing arotor, according to embodiments.

FIG. 10B is an illustrative flowchart of a method of multi-shotinjection molding a rotor.

FIGS. 11A-11F are illustrative perspective views of the steps depictedin the method of FIG. 10B. FIG. 11A depicts a mold closing and injectionprocess, FIG. 11B depicts a mold opening process, FIG. 11C depicts amold rotation process, FIG. 11D depicts a mold closing and injectionprocess, FIG. 11E depicts a mold opening process, and FIG. 11F depicts amold rotation and rotor ejection process.

FIG. 12 is an illustrative flowchart of a method of inspecting a rotor,according to embodiments.

FIG. 13A is an illustrative image of a rotor, according to embodiments.

FIG. 13B is a high contrast image of the rotor depicted in FIG. 13A.

FIG. 14A is an illustrative side view image of a reagent in a well of arotor, according to embodiments.

FIG. 14B is an illustrative plan view image of a reagent in a well of arotor, according to embodiments.

FIG. 15A is an illustrative side view of a container, according toembodiments.

FIG. 15B is an illustrative cross-sectional view of the containerdepicted in FIG. 15A.

FIG. 15C is an exploded view of the container depicted in FIG. 15A.

FIG. 15D is a perspective view of a rotor assembly including thecontainer depicted in FIG. 15A.

FIG. 15E is an exploded view of the rotor assembly depicted in FIG. 15D.

FIG. 16 is an illustrative perspective view of a weld nest, according toembodiments.

FIG. 17 is an illustrative exploded perspective view of a photomaskhousing, according to embodiments.

FIG. 18 is an illustrative perspective view of a rotor manufacturingsystem, according to embodiments.

DETAILED DESCRIPTION

Described herein are embodiments of rotor devices, systems, and methodsof use thereof. These systems and methods may be used to characterizeand/or quantitate a biological sample and permit evaluation of subjecthealth and/or diagnosis of a condition. For example, the rotorsdescribed herein may be configured for optical analysis of biologicalfluids, and in particular, for analyzing blood plasma after separatingit from cellular material using the rotor. More particularly, a rotormay be configured to separate plasma from whole blood, and/or adddiluent fluid to dilute the sample as desired, and distribute them intoseparate wells (e.g., cuvettes) configured for optical analysis of theircontents. Each well may contain one or more substances that may aidbiochemical analysis of the sample in the well. The sample may combinewith one or more of the reagents within one or more of the wells. Abiochemical reaction between the sample and reagent may produce anoptical effect when exposed to a light beam which may be detected andanalyzed. For example, by filling a set of wells with sample as therotor spins while optically analyzing the fluid in each well, the samplemay undergo a reaction or other change which results in a change in oneor more of color, fluorescence, luminescence, combinations thereof, andthe like, which may be measured by one or more of spectrophotometers,fluorometers, light detectors, combinations thereof and the like.

Each of the rotors (100, 200, 300, 400, 500, 600, 700) described indetail herein may receive a sample including, but not limited to, wholeblood that may contain one or more of blood, serum, plasma, urine,sputum, semen, saliva, ocular lens fluid, cerebral fluid, spinal fluid,amniotic fluid, and tissue culture media, as well as food and industrialchemicals, combinations thereof, and the like. Any of the rotors (100,200, 300, 400, 500, 600, 700) as described herein may be used with asuitable fluid analysis system (e.g., optical analyzer).

The devices disclosed herein may be suitable for performing a wide arrayof analytic procedures and assays. The analytic procedures may requirethat the sample be combined with one or more reagents so that somedetectable change occurs which may be combined with one or more reagentsso that some detectable change occurs which may be related to thepresence and/or amount of a particular component (analyte) orcharacteristic of the sample. For example, the sample may undergo areaction or other change which results in a change in color,fluorescence, luminescence, and the like, which may be measured by aspectrophotometer, fluorometer, light detector, and the like. In somecases, such assay procedures may be homogenous and not require aseparation step. In other cases, assay procedures may separate thesample (e.g., blood plasma) from a cavity or well after an immunologicalreaction has occurred. Any number of analytical methods may be adaptedfor use in the centrifugal rotor devices disclosed herein, dependingupon the particular sample being analyzed and component being detected.

In some embodiments, the rotor devices, reagents, systems, and methodsmay include one or more of the devices, systems, components, elements,compositions, and steps described in U.S. patent application Ser. No.07/532,524, filed on Jun. 4, 1990, and titled “APPARATUS AND METHOD FORSEPARATING CELLS FROM BIOLOGICAL FLUIDS,” and/or U.S. patent applicationSer. No. 07/678,824, filed on Apr. 1, 1991, and titled “APPARATUS ANDMETHOD FOR OPTICALLY ANALYZING BIOLOGICAL FLUIDS,” and/or U.S. patentapplication Ser. No. 07/678,823, filed on Apr. 1, 1991, and titled“CENTRIFUGAL ROTOR HAVING FLOW PARTITION,” and/or U.S. patentapplication Ser. No. 07/747,179, filed on Aug. 19, 1991, and titled“REAGENT COMPOSITIONS FOR ANALYTICAL TESTING,” and/or U.S. patentapplication Ser. No. 07/833,689, filed on Feb. 11, 1992, and titled“REAGENT CONTAINER FOR ANALYTICAL ROTOR,” and/or U.S. patent applicationSer. No. 07/783,041, filed on Oct. 29, 1991, and titled “SAMPLE METERINGPORT FOR ANALYTICAL ROTOR HAVING OVERFLOW CHAMBER,” and/or U.S. patentapplication Ser. No. 07/873,327, filed on Apr. 24, 1992, and titled“CRYOGENIC APPARATUS,” and/or U.S. patent application Ser. No.08/115,163, filed on Sep. 1, 1993, and titled “SIMULTANEOUS CUVETTESFILLING WITH MEANS TO ISOLATE CUVETTES,” and/or U.S. patent applicationSer. No. 08/124,525, filed on Sep. 20, 1993, and titled “ANALYTICALROTOR WITH DYE MIXING CHAMBER,” and/or U.S. patent application Ser. No.08/292,558, filed on Dec. 26, 1995, and titled “METHODS FOR PHOTOMETRICANALYSIS,” and/or U.S. patent application Ser. No. 08/350,856, filed onDec. 6, 1994, and titled “METHOD AND DEVICE FOR ULTRASONIC WELDING,”and/or U.S. patent application Ser. No. 10/840,763, filed on May 5,2004, and titled “MODIFIED SIPHONS FOR IMPROVING METERING PRECISION,”and/or International Patent Application Serial No. PCTUS2017/039460,filed on Jun. 27, 2017, and titled “DEVICES WITH MODIFIED CONDUITS,”each of which is hereby incorporated by reference in its entirety.

I. Devices

Described herein are devices that may be used in some embodiments of thevarious systems described. A rotor as described herein may include a setof cavities and wells. In some embodiments, one or more substances(e.g., reagent, lyophilized reagent) may be disposed in one or morewells of the rotor to facilitate sample analysis. For example, thereagents may be provided in dried form that may remain stable and intactduring transportation and storage. In some embodiments, the rotor maydefine openings, channels, cavities, conduits, wells, and/or otherstructures configured to provide one or more of separating cellularcomponents from the biological sample (e.g. whole blood), measuringpredetermined volumes of liquid sample (e.g. plasma), mixing the samplewith a predetermined diluent, and delivering the diluted sample to a setof wells for optical analysis. The fluid delivered to the set of wellsmay undergo one or more reactions within the set of wells that may aidcharacterization and quantification of one or more analytes within thefluid. The sample may be optically analyzed while present in the rotor,either with or without prior reaction.

The apparatus may be configured to be used with a fluid analysis systemto quantify and analyze characteristics of the sample. For example,optical measurements (e.g., absorbance) of each well may be performedwhile the rotor is spinning. A light beam of predetermined wavelengthmay be directed to pass through the set of wells. This light may bepartially absorbed by the products of the reaction between the reagentsand components of the fluid sample. The degree to which the light isabsorbed may depend on the concentration of the reaction product in thefluid sample. By comparing the intensity of the light transmittedthrough the well with a reference intensity, the concentration of agiven reaction product between the fluid and the reagent may becalculated. The concentration of the reaction product may be used tocalculate the concentration of a corresponding component in the samplefluid.

Rotor

In some embodiments, a rotor may include one or more features configuredto aid sample analysis. In particular, a rotor may include one or moresubstantially transparent layers and another layer being substantiallyabsorbent to infrared radiation (e.g., an opaque layer). For example, anopaque layer may be composed of a carbon black and acrylic compound thatmay be black in color. The opacity formed by this combination mayprovide a consistent contrasting background with a biological sampleplaced in the rotor, unlike a transparent rotor. This may aid a user(e.g., operator, technician) in applying and verifying the sample in therotor, as well as inspection of the rotor welds of the different layers.Moreover, the rotor layers may be coupled together using laser weldingtechniques that may reduce manufacturing cycle times and improve rotorquality. For example, laser welding may increase weld consistency andimprove rotor shape (e.g., flatness of the rotor).

FIG. 1A is an illustrative plan view of a rotor (100) while FIG. 1B isan illustrative bottom view of the rotor (100). The rotor (100) mayinclude a substantially transparent first layer (101) with a first side(e.g., underside) of the second layer (102) coupled to the first layer(101). The first layer (101) and the second layer (102) may collectivelydefine a set of wells (130). For example, at least a base portion (e.g.,bottom portion) of each well of the set of wells (130) may be formed bythe first layer (101). The opening (e.g., top portion) of each wellopposite the base portion of the set of wells (130) may be defined bythe second layer (102). Sidewalls of each well of the set of wells (130)may be generally cylindrical and may be formed by either the first layer(101), the second layer (102), or some combination thereof. In someembodiments, each well of the set of wells (130) may have a depth ofbetween about 1.0 mm and about 10 mm, and a diameter of about 5 mm orless. In some embodiments, the rotor (100) may include between 5 wellsand 50 wells. In some embodiments, each well of the set of wells (130)may define a volume of between about 1 μL and about 40 μL. In someembodiments, adjacent wells of the set of wells (130) may be spacedapart by between about 1 mm and about 30 mm. The set of wells of a rotorare described in more detail with respect to FIGS. 3A-3B. In FIG. 1A,the second layer (102) is shown disposed above the first layer (101).

In some embodiments, at least a portion of the second layer (102) may besubstantially absorbent for infrared radiation. For example, the secondlayer (102) may be opaque (e.g., black), which is not illustrated in thefigures for the sake of clarity. Likewise, the transparency of anytransparent portion of a rotor described herein is not depicted for thesake of clarity. In some embodiments, at least a portion of the secondlayer (102) may be substantially absorbent to at least one ofmid-infrared radiation and near-infrared radiation. Infrared radiationmay have a wavelength between about 700 nm and about 1 mm. Mid-infraredradiation may have a wavelength between about 3 μm and about 8 μm.Near-infrared radiation may have a wavelength between about 0.75 μm andabout 1.4 μm. Visible light may have a wavelength between about 400 nmand about 700 nm. Ultraviolet light may have a wavelength between about10 nm and about 400 nm. In some embodiments, at least a portion of thesecond layer (102) may be substantially absorbent to at least 940 nmwavelength radiation.

As used herein, the terms ‘transparent’, ‘transparency’, and variantsthereof may be understood as light transmission at a predeterminedwavelength and/or range of wavelengths of chemical importance (such asfor laser welding) of about 10% or more through its layer while theterms ‘opaque’, ‘opacity’, ‘opaqueness’, and variants thereof mayinclude light transmission at the predetermined wavelength and/or rangeof wavelengths of about 10% or less through its layer. For example,acrylic may generally be considered transparent as it provides about 90%UV wavelength transmission. Transparent plastics formed using laserwelding may retain their transparency in wavelengths. Furthermore,opaqueness of a material may correspond to energy absorption at apredetermined wavelength and/or predetermined range of wavelengths. Asused herein, a material substantially absorbent to infrared radiationcorresponds to a material that may absorb infrared radiation (of apredetermined range of wavelengths and power) to transition the materialfrom a solid phase to a molten phase within a predetermined period oftime.

The first layer (101) and the second layer (102) may furthercollectively define other structures of the rotor (100) (e.g., cavities,channels, holes, protrusions, projections) as described in more detailherein. For example, the second layer (134) may define one or moreportions of a set of arcuate cavities (110, 112, 114), a set of channels(120, 122), a set of inlets (132, 134), and a set of reflectors (140).In some embodiments, the set of channels (120, 122) may establish afluid communication path between the arcuate cavity (110) and the set ofwells (130, 150, 152).

Each well of the set of wells (130) may be coupled to the channel (120)by a respective inlet (132, 134). Each well of the set of wells (130)may be configured to fill in series. That is, the rotor (100) mayinclude a set of high density, series filled cuvettes. In someembodiments, each inlet of the set of inlets may have the samedimensions. In other embodiments, each inlet of the set of inlets mayhave different dimensions. For example, a width of a first set of inlets(132) may be less than a width of a second set of inlets (134). Thedifferent inlet dimensions may allow each of the wells (130) to fillwith fluid at different velocities (i.e., due to acceleration) of thespinning rotor (100). The wider width of the second set of inlets (134)may be configured to accommodate bidirectional flow of liquid in onedirection and gas in the opposite direction at relatively lowrevolutions per minute (e.g., under about 4,000 RPMs), as described inmore detail herein. In some embodiments, a width of the set of inletsmay be between about 0.25 mm and about 3.0 mm, a length of the set ofinlets may be between about 0.5 mm and about 6.0 mm, and a depth of theset of inlets may be between about 0.1 mm and about 0.25 mm.

In some embodiments, arcuate cavities (112, 114) may correspond to arespective metering chamber and mix chamber. For example, diluent fluidmay be received and held in the metering chamber (112) after a diluentcup has been opened. The mix chamber (114) may be configured to becoupled to the metering chamber (112) and the arcuate cavity (110) suchthat fluid from each of those cavities may combine within the mixchamber (114) (e.g., sample and diluent). In some embodiments, the setof wells may include a sample check well (150) and a red blood cell(RBC) well (152). The sample check well (150) may be used as a gauge ofwhether enough sample has been input into the rotor (100). For example,an unfilled or incompletely filled sample check well (150) may indicatethat insufficient sample has been inserted into the rotor (100) toperform fluid analysis. The RBC well (152) may be configured to receiveand hold red blood cells of the sample. For example, a whole bloodsample may be separated into red blood cells held in the RBC well (152)and plasma that may fill the set of wells (130).

In some embodiments, the first layer (101) may be substantiallytransparent to one or more of ultraviolet light, visible light, andinfrared radiation. In some embodiments, the first layer (101) and thesecond layer (102) may be independently composed of one or more ofacrylic, polycarbonate, cyclic olefin copolymers (COC), polystyrene,acrylonitrile butadiene styrene (ABS), and other materials transparentto ultraviolet light.

In some embodiments, the second layer (102) may include at least about0.1% by weight of at least one of an organic and inorganic pigment. Forexample, the second layer (102) may include between about 0.2% to about0.4% by weight of carbon black.

Organic pigments may include carbon black and laser absorbingcompositions. Carbon black may have an absorption range of between about500 nm and about 2200 nm. Carbon black may have an optical penetrationdepth for near-infrared radiation wavelengths of between about 10 μm andabout 100 μm based on concentration (e.g., about 0.1% and more by weightat 940 nm). In some embodiments, the laser absorbing composition may besubstantially absorbent to radiation between about 700 nm to about 8 μm.For example, Clearweld® and Lumogen® may have an absorption range ofbetween about 700 nm and about 1100 nm.

Inorganic pigments may include copper phosphates and indium tin oxide(ITO). Copper phosphates may have an absorption range of between about900 nm and about 1600 nm. ITO may have an absorption range above about1000 nm.

The rotor devices as described herein may include an opening (e.g.,receptacle) configured to be mounted on a system, such as a centrifuge,for spinning. The centrifuge may include, for example, a vertical driveshaft on which the rotor may be mounted. However, a rotor may haveinherent or residual imbalances due to one or more of rotor design andfluid flow within the rotor. For example, a biological sample may beconfigured to flow through different cavities, chambers, and channels ofa rotor throughout a centrifugation process. In some cases, a rotor maybe configured to be generally balanced when fluid fills a set of wells,but may be unbalanced when the sample is input and held in a holdingchamber (e.g., arcuate cavity). Accordingly, the rotor may generateundesirable noise throughout a centrifugation process that may reducethe desirability of rotor use in point-of-care settings.

As shown in FIG. 1B, a first side (e.g., underside, bottom side) of thesecond layer (102) may include a set of arcuate protrusions (160) and ahole (180). The set of arcuate protrusions (160) may have apredetermined shape, number, position, and mass distribution configuredto offset a center of mass of the rotor (100) from a center of the rotor(100). Additionally or alternatively, the second layer (102) may includea set of recessed portions (162) having a predetermined shape, number,position, and volume. For example, the set of recessed portions (162)and arcuate protrusions (160) may have one or more of an arcuate,radial, oblong, secant, and linear shape. In some embodiments, the setof recessed portions (162) may be parallel and arcuate. In someembodiments, a center of mass of a rotor may be configured to be betweenup to about 0.5 mm from a center of the rotor. In this manner, thecenter of mass of the rotor may be closer to the center of mass of therotor having fluid flow throughout a centrifugation process. This mayaid overall noise reduction during centrifugation of the rotor (100),especially under different centrifugation speeds.

In some embodiments, the first layer (101) and/or the second layer (102)may be formed using injection molding (e.g., multi-shot molding) and/ormachining as described in more detail herein. In some embodiments, thefirst layer (101) and/or the second layer (102) may be bonded to theother layers of the rotor (100) using one or more of ultrasonic welding,laser welding, adhesives (e.g., adhesive tape), and/or solvent bonding.

For example, laser welding may use one or more of a semiconductor diodelaser, solid-state Nd:YAG laser, and fiber laser. A diode laser maygenerate a light beam having a wavelength between about 800 nm and about2000 nm (e.g., about 940 nm, about 980 nm). A Nd:YAG laser may generatea light beam having a wavelength at about 1064 nm. A fiber laser maygenerate a light beam having a wavelength between about 1030 nm andabout 1620 nm.

In some embodiments, the rotor (100) may have a diameter of betweenabout 40 mm and about 120 mm and a thickness of between about 10 mm andabout 30 mm, including all values and sub ranges in-between.

FIGS. 2A and 2B are illustrative exploded views of a rotor assembly(200), according to other embodiments. The rotor assembly (200) mayinclude a rotor structurally and/or functionally similar to the rotors(100, 300, 400, 500, 600, 700) as described herein. For example, therotor assembly (200) may include a substantially transparent first layer(201) coupled to a first side (e.g., underside) of the second layer(202). The first layer (201) and the second layer (202) may collectivelydefine a set of wells (230). In some embodiments, at least a portion ofthe second layer (202) may be substantially absorbent to infraredradiation. In some embodiments, at least a portion of the second layer(202) may be substantially absorbent to one or more of mid-infraredradiation and near-infrared radiation. For example, at least a portionof the second layer (202) may be substantially absorbent to at least 940nm wavelength radiation. The first layer (201) and the second layer(202) may further collectively define other structures of the rotor(200) (e.g., cavities, channels, holes, protrusions, projections) asdescribed in more detail herein. For example, the second layer (102) maydefine one or more portions of an arcuate cavity (210) and a set ofchannels (220). In some embodiments, the set of channels (220) mayestablish a fluid communication path between the arcuate cavity (210)and the set of wells (230).

In some embodiments, the second layer (202) may include at least about0.1% by weight of carbon black. For example, the second layer (202) mayinclude between about 0.2% to about 0.4% by weight of carbon black. Insome embodiments, the first layer (201) and/or the second layer (202)may be formed using injection molding (e.g., multi-shot molding) and/ormachining as described in more detail herein. In some embodiments, thefirst layer (201) and/or the second layer (202) may be bonded to theother layers of the rotor (200) using one or more of ultrasonic welding,laser welding, adhesives (e.g., adhesive tape), and/or solvent bonding.For example, laser welding may use one or more of a semiconductor diodelaser, solid-state Nd:YAG laser, and fiber laser.

The rotor assembly (200) may include a third layer (203) that may becoupled to a second side (e.g., top side) of the second layer (202). Thethird layer (203) may define an opening (240) configured to receive afluid such as blood. The third layer (203) may be substantiallytransparent. The channel (220) may establish a fluid communication pathbetween the opening (240) and the set of wells (230). The opening (240)of the third layer (203) may be configured to receive a sample. Forexample, the sample may be pipetted, injected through a membrane, andpoured. The opening (240) may have any suitable shape and/or size toreceive the sample. The third layer (203) may be coupled to the secondlayer (202) using laser welding. For example, laser welding may use oneor more of a semiconductor diode laser, solid-state Nd:YAG laser, andfiber laser.

In some embodiments, the rotor assembly (200) may include a fourth layer(204) (e.g., sample holder). A rotor may be removably held by a fourthlayer (204) to aid in handling, processing, and identification of arotor and/or sample. The fourth layer (204) coupled to the rotor may beplaced by a user into a fluid analysis system for automated processingof the sample. The fourth layer (204) may be useful in providingphysical support and protection to the rotor.

The fourth layer (204) may be coupled to an external surface of a thirdlayer (203). For example, the fourth layer (204) may include a set ofprotrusions (294) (see FIG. 2B) configured to fit within correspondingholes (296) of the third layer (203). The fourth layer (204) may includea set of portions (e.g., outer and inner circumference, edges) for auser to grasp without touching the other rotor layers (201, 202, 203)and potentially affecting the optical qualities of the rotor assembly(200). A diameter of the fourth layer (204) may be greater than adiameter of the rotor. The fourth layer (204) may define a set ofopenings (292) configured to allow unimpeded light transmission throughthe set of wells (230) and/or reduce weight. The fourth layer mayfurther function as a shield against sample fluid that may spin out ofthe opening of a rotor during centrifugation. The fourth layer (204) maybe configured to hold the rotor assembly (200) at a fixed positionrelative to the fourth layer (204) while allowing unimpeded lighttransmission through the set of wells (230). FIG. 2C depicts theassembled rotor assembly (200). The fourth layer (204) may be opaque.

In some embodiments, the fourth layer (204) may include one or moreidentifiers (290) such as a barcode, QR code, and one or more fiducials(e.g., colored/opaque points, ruler, slits, landmarks, markers),combinations thereof, and the like. For example, an arcuate barcode maybe disposed along an outer circumference of the fourth layer (204)(e.g., on a side of the cover (204) facing away from the third layer(203)). The identifiers may be used for identification and processing ofthe rotor assembly (200).

In some embodiments, the first layer (201) and the third layer (203) maybe substantially transparent to one or more of ultraviolet light,visible light, and infrared radiation. In some embodiments, the firstlayer (201), the second layer (202), the third layer (204), and thecover (204) may be independently composed of one or more of acrylic,polycarbonate, cyclic olefin copolymers (COC), polystyrene, andacrylonitrile butadiene styrene (ABS) and/or the like. Although thedevice (200) shown in FIGS. 2A-2C include three layers, it should beappreciated that any of the rotors described herein may be formed usingmore or less layers. In some embodiments, a layer substantiallyabsorbent to infrared radiation may be printed on a transparent firstlayer. For example, a layer of carbon black or a laser absorbingcomposition may be printed over a surface of a transparent first layer(e.g., rotor base including the wells, channels, and cavities describedherein).

FIG. 3A is a cross-sectional side view and FIG. 3B is a detailedcross-sectional side view of a well (330) of a rotor (300). The rotor(300) may be structurally and/or functionally similar to the rotor (100,200, 400, 500, 600, 700) as described herein. The rotor (300) mayinclude a substantially transparent first layer (301) coupled to asecond layer (302). The first layer (301) and the second layer (302) maycollectively define a set of wells (330). Each well of the set of wells(330) may be formed along a periphery of the rotor (300). For example,the set of wells (330) may follow a circumference of the rotor (300). Insome embodiments, the set of wells (330) may include a generallycylindrical shape as described in more detail herein. For example, asshown in FIG. 3B, each well (330) may be defined by an opening (338) inthe second layer (302) while the sidewalls (334) and a base portion(332) may be formed in the first layer (301). Alternatively, in someembodiments, one or more portions of the sidewalls (334) may be formedby the second layer (302). As shown in the detailed cross-sectional sideview of FIG. 3B, the sidewall (334) may include a first sidewall portion(335) and a second sidewall portion (336).

In some embodiments, a diameter of the opening for each well of the setof wells may be greater than a diameter of the base of each well of theset of wells. In some embodiments, the well (330) may taper inward froman opening (338) toward the base portion (332). In some embodiments, anintermediate portion of the well may taper more than the end portions ofthe well (330). For example, the first sidewall portion (335) may taper(351) up to about 2°. The second sidewall portion (335) may taper (353)between about 3° and about 9°. The opening (338) may taper (355) up toabout 2°. This well (330) configuration may aid coupling between thefirst layer (301) and the second layer (302) when these layers arepressed together in an injection molding process. For example, thetapered sidewall surfaces may be configured as a shut off for a two-shotinjection molding process that may prevent a carbon-filled material frominfiltrating into a transparent material. That is, the shut off providedby the tapered surface may establishes a boundary between the secondmaterial and the first material.

An incident light beam may be configured to be transmitted through thewell (330) without passing through the sidewalls (334). In someembodiments, the opening may have a depth between about 0.25 mm and 7mm, and a diameter between about 1 mm and about 5 mm. In someembodiments, the first sidewall portion may have a depth between about 2mm and about 6 mm.

In some embodiments, at least a portion of the second layer (302) may besubstantially absorbent to infrared radiation. For example, the secondlayer (302) may be opaque (e.g., black). In some embodiments, at least aportion of the second layer (302) may be substantially absorbent to oneor more of mid-infrared radiation and near-infrared radiation. Forexample, at least a portion of the second layer (302) may besubstantially absorbent to at least 940 nm wavelength radiation.

The first layer (301) and the second layer (302) may furthercollectively define other structures of the rotor (300) (e.g., cavities,channels, holes, protrusions, projections) as described in more detailherein. For example, as shown in FIG. 3A, the second layer (302) maydefine a hole (380) within a center of the second layer (302). In someembodiments, the first layer (301) may be substantially transparent toone or more of ultraviolet light, visible light, and infrared radiation.In some embodiments, the first layer (301) and the second layer (302)may be independently composed of one or more of acrylic, polycarbonate,cyclic olefin copolymers (COC), polystyrene, acrylonitrile butadienestyrene (ABS), and the like. In some embodiments, the second layer (302)may include at least about 0.1% by weight of carbon black. For example,the second layer (302) may include between about 0.2% to about 0.4% byweight of carbon black.

In some embodiments, the first layer (301) and/or the second layer (302)may be formed using injection molding (e.g., multi-shot molding) and/ormachining as described in more detail herein. In some embodiments, thefirst layer (301) and/or the second layer (302) may be bonded to theother layers of the rotor (100) using one or more of ultrasonic welding,laser welding, adhesives (e.g., adhesive tape), and/or solvent bonding.For example, laser welding may use one or more of a semiconductor diodelaser, solid-state Nd:YAG laser, and fiber laser.

Inlet

FIGS. 4A-4B are detailed plan views of a set of wells, a set of inlets,and a set of reflectors of a rotor. In some embodiments, the rotors asdescribed herein may define a set of generally radial inlets (e.g.,channels) coupled between a respective well and a channel of the rotor.The inlets may be configured to allow liquid phase and gas phasecommunication between a well and the channel. For example, as the rotoris spun (e.g., by a centrifuge), fluid may enter the well through arespective inlet coupled to a channel and arcuate cavity (e.g., holdingchamber, collection chamber). Some of the inlet channels may include adiscrete first flow path for fluid to enter the well and a discretesecond flow path for gas to exit the well. This may allow gas in thewells to escape, thus limiting the creation of bubbles in the well asthe wells are filled.

As shown in the detailed plan view of the rotor (400) in FIG. 4A, therotor (400) may include a layer (402) structurally and/or functionallysimilar to the second layer (102, 202, 302, 502, 702) as describedherein such as a substantially opaque layer that may be absorbent toinfrared radiation. The layer (402) may define a set of structuresincluding one or more of a channel (420), a set of wells (430, 433), anda set of inlets (432, 434) coupled therebetween. Each inlet of the setof inlets (432, 434) may correspond to a different well of the set ofwells (430, 433). Each inlet of the set of inlets (430, 433) mayestablish a fluid communication path between the channel (420) and itscorresponding well. The layer (402) may further define a set ofreflectors (440) with each reflector disposed between adjacent wells(430).

In some embodiments, a width of at least one inlet of the set of inlets(432, 434) may be greater than a width of the channel (420). In someembodiments, the set of inlets (432, 434) may include a first subset ofinlets (432) (see FIG. 4A) and a second subset of inlets (434) (see FIG.4B). A width of each inlet of the first subset of inlets (432) maydiffer from a width of each inlet of the second subset of inlets (434).The second subset of inlets (434) may be configured to allow venting offluid (e.g., liquid phase and gas phase) within the channel (420) at lowrevolutions per minute (RPMs). For example, bidirectional flow of fluidwithin the second subset of inlets (434) may occur during spinning ofthe rotor (400) between about 500 RPMs and about 2500 RPMs. The inletsof the first subset of inlets (432) may accommodate bidirectional fluidflow for rotors spinning above about 4000 RPMs.

In some embodiments, a subset of the wells (430, 433) coupled to asecond subset of inlets (434) may be located along the channel (420)adjacent to or near the channel (422) (e.g., conduit). The wells (430,433) adjacent to or near the conduit (422) may be configured to fillbefore the other wells (430) disposed farther away from the conduit(422). When the rotor is spun at relatively low RPMs (e.g., under about4000 RPMs), bidirectional fluid flow may not occur using inlets having awidth of the first set of inlets (432). For example, fluid entering awell (430) coupled to a first subset of inlets (432) during spinning ofthe rotor at about 1000 RPM may trap air bubbles within the inlet (432)and result in incomplete filling of the well (430) because the inlet isnot wide enough to allow simultaneous liquid phase and gas phase flow atthat RPM. However, the wider inlets having a width of the second set ofinlets (434) may be configured to accommodate bidirectional flow ofliquid and gas at relatively low revolutions per minute, therebyallowing a greater number of wells (430) to be utilized in the rotor(400). In some embodiments, the set of inlets may include a set ofdifferent widths including 1, 2, 3, 4, 5, 6, or more widthscorresponding to a set of spinning rotor RPMs. The inlets (432, 434)having different widths may be provided in any order along the channel(420).

In some embodiments, wells (430, 433) coupled to the second subset ofinlets (434) do not include a reagent. In some embodiments, a width ofthe set of inlets may be between about 0.25 mm and about 3.0 mm, alength of the set of inlets may be between about 0.5 mm and about 6.0mm, and a depth of the set of inlets may be between about 0.1 mm andabout 0.25 mm.

It should be appreciated that relatively wide inlet widths for wells atany given RPM may require more sample volume to properly fill the wellsand may increase the risk of cross-contamination of reagent and/orsample between wells. In some embodiments, each well including at leastone reagent may have an inlet width of the first subset of inlets (432)and each well without a reagent may have an inlet width of the secondsubset of inlets (434).

Reflector(s)

In some embodiments, a rotor as described herein may include a set ofreflectors (e.g., reflective surfaces) positioned radially inward from aset of wells. The set of reflectors may be configured to receive andreflect a light beam used as a timing signal for optical analysis of anadjacent well. A light beam received and reflected by the reflector maybe received by a detector. A control device may process the light signalreceived from the reflector to activate a radiation source to guide alight beam configured to pass through an optical path of a well. Forexample, the light beam received from the reflector may indicate thatthe well may soon pass between the radiation source and detector (e.g.,within a few microseconds). FIG. 4C is a cross-sectional side view of areflector (440) depicted in FIG. 4A. Each reflector of the set ofreflectors (440) may be disposed between adjacent wells of the set ofwells (430). Each reflector of the set of reflectors (440) may define aprism-shaped cavity and may be formed in a substantially transparentlayer of the rotor (e.g., first layer (101, 201, 301) as described indetail herein. Each prism-shaped cavity may include a reflectivesurface. Each reflector of the set of reflectors may be configured toreceive and deflect a light beam by about 90° (although an angledifferent than 90° may be used as well). For example, the reflectivesurface may be oriented at about a 45° angle to a rotational axis of therotor (e.g., an axis perpendicular to a plane of the rotor) and may beconfigured to generate total internal reflection at a rotor-airinterface.

In some embodiments, a polish may be disposed over a reflective surfaceof each prism-shaped cavity of the set of reflectors (440). A reflectivesurface of the reflector may include a polish having a surface roughnessaveraging between about 0 and about 3. In some embodiments, a width of areflector may be between about 0.5 mm and about 2.5 mm, a length of thereflector may be between about 2 mm and about 3 mm, and an angle of areflective surface relative to a plane of the rotor may be between about30 degrees and about 60 degrees.

Arcuate Cavity

The rotors as described herein may be configured to receive a samplethrough an opening leading into a sample receiving chamber. For example,the sample may be input into the rotor using a pipette. A pipette may beconfigured to output a sample through a narrow tip at high velocity,which may generate one or more of air bubbles and sample overflow wheninput into some conventional rotors. FIG. 5A is a detailed plan view ofan arcuate cavity (510) (e.g., sample receiving chamber) of a rotor(500). FIG. 5B is a detailed cross-sectional side view of the arcuatecavity (510) depicted in FIG. 5A. The rotor (500) may include asubstantially transparent first layer (501) coupled to a substantiallyopaque (e.g., substantially absorbent to infrared radiation) secondlayer (502). The arcuate cavity (510) may be configured to receive andhold a fluid prior to delivery to a set of wells (530) of the rotor(500).

The second layer (502) may further define a channel (520). The firstlayer (501) and the second layer (502) may further collectively defineother structures of the rotor (500) (e.g., cavities, channels, holes,protrusions, projections) as described in more detail herein. Forexample, the second layer (502) may define one or more portions of a setof channels (520, 522), a set of inlets (532), a set of wells (530), anda set of reflectors (540), as described in detail herein. A fluidcommunication path may be established between the opening in the rotor(500), the arcuate cavity (510), set of channels (520, 522), set ofinlets (532), and set of wells (530). The arcuate cavity (510) may beconfigured for fluid communication between the opening and the set ofchannels (520).

As shown in FIG. 5A, a width of the arcuate cavity (510) may narrow in aproximal-to-distal direction (e.g., in a clockwise direction in FIG.5A). In some embodiments, the arcuate cavity (511) may have awidth-to-depth ratio between about 0.8 to about 1.2. In thisconfiguration where the width and depth of the arcuate cavity (510) aregenerally similar, the arcuate cavity may reduce the generation of airbubbles and sample back-up when sample is introduced into the arcuatecavity (510) using a pipette. For example, a sample of whole blood maybe pipetted into the arcuate cavity through a sample port of the samplereceiving chamber.

Moreover, the second layer (502) of the rotor (500) may form a width ofthe arcuate cavity (510) such that a “floor” of the arcuate cavity (510)is substantially opaque. Consequently, an easily visible contrast may beformed when sample such as whole blood is received in the arcuate cavity(510) that may aid filling of the sample into the rotor (500).

A substantially transparent third layer (not shown for the sake ofclarity) may be coupled to the second layer (502) and form a “ceiling”of the arcuate cavity (510). The third layer may define an opening (notshown) aligned with the arcuate cavity (510) such that the arcuatecavity (510) may receive fluid through the opening. In some embodiments,the arcuate cavity (510) may have a depth of between about 1.0 mm andabout 10 mm and may define a volume of between about 50 μL and about 200μL. This may aid even distribution and filling of the arcuate cavity(510) without overflow of sample out of an opening in the arcuatecavity.

In some embodiments, the arcuate cavity may be configured to hold afluid, mix a fluid with another substance, generate one or more chemicalreactions, and/or be used to characterize the fluid and/or othersubstances in the arcuate cavity. In some embodiments, fluid may bemixed with a reagent such as a diluent or a dye within the arcuatecavity. For example, a reagent may be disposed in the arcuate cavity ina liquid or solid form (e.g., bead, pellet, and the like). The reagentmay be attached (e.g., coated) to a surface of the arcuate cavity suchas a sidewall, and/or attached to a solid matrix. Chemical reactionswithin the arcuate cavity may include heterogeneous immunochemistryreactions and chemical reactions having discrete steps. For example, aprecipitate may form and settle in the arcuate cavity. The supernatantmay thereafter be decanted.

In some embodiments, the fluids in the arcuate cavity may be opticallyanalyzed to characterize the fluid. For example, the fluid in thearcuate cavity exposed to a light beam may generate an optical effectthat may be detected and analyzed in a manner analogous to opticalanalysis of the set of wells. In particular, one or more of fluiddensity, height, and volume may be measured. Characteristics of thefluid in the arcuate cavity may be compared to fluid in the set ofwells.

Conduit

FIG. 6 is a detailed plan view of a channel (622) of a rotor (600). Therotor (600) may define a set of channels such as a conduit (622) (e.g.,siphon) including an inlet (623), U-shaped portion (625), and outlet(627). The conduit (622) may be configured to couple a sample receivingcavity to a mixing cavity. The conduit (622) may be configured todeliver a predetermined volume of fluid (e.g., plasma) through a fluidcommunication path (e.g., between an opening and a set of wells) whenthe rotor is stationary and to prevent fluid flow when the rotor isspinning. That is, one or more conduits of a rotor may be configured todeliver metered volumes of fluid to a desired cavity in the rotor.

In some embodiments, the conduit (622) may be configured such that fluiddrawn into the conduit (625) through the inlet (623) does not flowthrough the U-shaped portion (625) (e.g., elbow) when the rotor isspinning. After the rotor stops spinning, capillary forces may drawfluid through the U-shaped portion (625). If the rotor is spun again,then centrifugal force may advance the fluid out of the outlet (627).The U-shaped portion (625) of the conduit (622) may be closer to acenter of the rotor (600) (e.g., more radially inward) than the inlet(623) and outlet (627). The outlet (627) may extend closer to aperiphery of the rotor (600) than the inlet (623) (e.g., more radiallyoutward).

In some embodiments, the rotor may include at least one conduit. Forexample, the rotor may include three conduits configured to couple thesample receiving chamber to the mixing chamber, the metering chamber tothe mixing chamber, and the mixing chamber to the channel.

Container Puncture Mechanism

FIG. 7A is an illustrative exploded view of a rotor assembly (700) andFIG. 7B is a detailed perspective view of a third layer (703) of therotor assembly (700). The rotor assembly (700) may include a rotorstructurally and/or functionally similar to the rotors (100, 200, 300,400, 500, 600) as described herein. The rotor assembly (700) may includea first layer (701) coupled to a first side (e.g., underside) of asecond layer (702). The first layer (701) and the second layer (702) maycollectively define a set of wells (730). The rotor assembly (700) mayinclude a third layer (703) that may be coupled to a second side (e.g.,top side) of the second layer (702). The third layer (703) may define anopening (740) configured to receive a fluid such as blood. The thirdlayer (703) may include a set of protrusions (710) extending toward thesecond layer (702). The set of protrusions (710) may take include anynumber and shape suitable for puncturing a container (750) disposedwithin a cavity (752) of the second layer (702) of the rotor assembly(700). The cavity (752) may define a hole (e.g., receptacle) configuredto receive, for example, a spindle of a centrifuge. For example, thecavity (752) may receive a post of a spindle which may be configured toengage the container (750) and advance the container toward the set ofprotrusions (710) of the third layer (703). The container (750) may besized and positioned to be held in the cavity (752) and disposed overthe hole.

In some embodiments, the rotor assembly (700) may include a fourth layer(704) that may be coupled to an external surface of a third layer (703).The fourth layer (704) may include a set of protrusions (794) configuredto fit within corresponding holes (796) of the third layer (703). Thefourth layer (704) may define a set of openings (792) configured toallow unimpeded light transmission through the set of wells (730) and/orreduce weight.

In some embodiments, the rotor (700) may be configured to release fluid(e.g., diluent) held in a container (750) in response to the containerbeing advanced toward the third layer (703) and away from the secondlayer (702). The container (750) may be held in a cavity (752) of therotor (700). A portion of the container (750) may be sealed with amembrane (e.g., foil seal) on a first side and a rigid surface on asecond side opposite the first side. In some embodiments, the membranemay be configured to be punctured by the set of protrusions (710) of thethird layer (703) of the rotor assembly (700) when the container (750)is advanced toward the third layer (703) such as, for example, when therotor (700) is mounted to a centrifuge (not shown) and a portion of thecentrifuge pushes the container (750) into the protrusions (710). Insome embodiments, when a rotor is placed on a spindle, the spindlecontacts and pushes up on a bottom surface of the container (750).

Container

In some embodiments, a container may be configured to hold diluent, forma liquid-tight seal against the cavity its disposed in, and slide withinthe cavity when pushed by an external force. In some embodiments, thecontainer may be cylindrical. FIG. 15A is an illustrative side view of acontainer (1500) including a body (1510) and a seal (1520) (e.g.,elastomeric seal). FIGS. 15D and 15E are perspective views of a rotorassembly and the container. One or more portions of a circumference of acontainer (1500) may include an elastomeric (e.g., rubber) seal (1520)that may be configured to engage with a wall in a cavity (1530) of rotor(1550) through an interference fit. For example, the elastomeric seal(1520) may be configured such that the container (1510) at rest remainsat a fixed position within the rotor (1550) and forms a watertight seal.However, when engaged by a spindle or other protrusion, the container(1500) may be advanced upward towards a third layer (not shown) of therotor (1550) while maintaining a seal with the rotor (1550). When thecontainer (1500) is punctured by protrusions, the elastomeric seal(1520) may be configured to prevent liquid from flowing along the sidesof the container (1500) and over a bottom surface of the cavity (1530).Thus, an elastomeric seal (1520) of a container (1500) may ensure fluidflow from the container (750) to an adjacent metering chamber withoutloss of fluid. The fluid within a container (1500) may flow out of thecontainer (1500) by one or more of centrifugal force and gravity.

In some embodiments, a container (1500) may be composed of a fluidbarrier material including plastics and other polymeric materials suchas high density polyethylene. The container (1500) may be manufacturedby one or more of molding, pressure forming, vacuum forming, andmachining. For example, the container may be formed using a two-shotinjection molding process. FIG. 15C is an exploded perspective view of abody (1510) and seal (1520) of the container (1500).

The container body (1510) may define one or more cavities (e.g.,compartments, chambers), as shown with one cavity in FIG. 15B. Eachcavity of the container (1500) may have the same or different contents.For example, a first cavity may have a fluid (e.g., diluent) while asecond cavity may have a lyophilized reagent. Each cavity may containthe same or different fluid. For example, two cavities of a container(750) may be coupled to an arcuate cavity of the second layer (702) inwhich a set of fluids (e.g., diluent, sample, and a marker compound) aremixed.

The membrane (e.g., foil seal) may be laminated with polyethylene oranother plastic. Each cavity of the container (1500) may have its ownmembrane. The container (1500) may be manufactured by filling thecontainer (1500) with a predetermined volume of fluid (e.g., diluent,reagent) and closing the container (1500) by, for example, one or moreof heat sealing and ultrasonic welding.

Diluent

The rotors as described herein may include a diluent to be mixed with asample (e.g., fluid, plasma). A diluent may be disposed within the rotoras described herein with respect to a diluent container or input into anarcuate cavity of the rotor. In some embodiments, a diluent may includean isotonic concentration of a compound which does not interfere withthe analysis of a sample. The diluent may include one or more of asaline solution (e.g., 0.5% NaCl in water), phosphate buffered solution,Ringer's lactate solution, tetramethylammonium acetate, inositol, markercompounds, combinations thereof, and the like. For example, a diluentmay have substantially no buffer capacity at the pH of a particularassay.

Reagent

A reagent may be prepared by forming an aqueous solution that isdispensed uniformly as drops into a cryogenic liquid, and lyophilizingthe frozen drops. The cryogenic liquid may be, for example, non-agitatedliquid nitrogen. The reagent may include one or more of diluents,aqueous solutions, buffers, organic compounds, dehydrated chemicals,crystals, proteins, solvents, and marking compounds. Marking compoundsmay include a dye, fluorescent and phosphorescent substances,radioactive labelling materials, enzymes, biotin, and immunologiccompounds.

In some embodiments, a reagent may have a generally spherical shapehaving a diameter between about 1.0 mm and about 2.3 mm and have acoefficient of weight variation less than about 3%. In some embodiments,a lyophilized reagent may include one or more of a surfactant in aconcentration sufficient to inhibit bubble formation when the reagentdissolves, and a filler in a concentration sufficient to facilitateformation of a chemical lattice capable of conducting water into thereagent. For example, the surfactant may be a non-ionic detergent suchas octoxynol 9 or polyoxyethylene 9 lauryl ether. The concentration of asurfactant in the reagent may be configured such that the concentrationin the reconstituted reagent is between about 0.08 g and about 3.1 g per100 ml. The chemical lattice formed by the filler may allow the reagentto quickly and completely dissolve in a sample solution or diluent. Insome embodiments, a filler may include one or more of polyethyleneglycol, myo-inositol, polyvinylpyrrolidone, bovine serum albumin,dextran, mannitol, sodium cholate, combinations thereof, and the like.The filler may have a concentration between about 10% and about 50% bydry weight.

In some embodiments, photometrically detectable marker compounds may beconfigured to generate a color reaction and may include1,1′,3,3,3′,3′-hexamethylindotricarbocyanine iodide and 1,1′-bis(sulfoalkyl)-3,3,3′,3′-tetramethylindotricarbocyanine salts. Markercompounds may be used, for example, to determine dilution in situ andmay include photometrically detectable compounds. A concentration of themarker may be photometrically determined by comparing the absorbance ofthe diluted sample at a predetermined wavelength to a reference solutionof known concentration. The ratio of the concentrations of the markerbefore and after mixing with a sample may be used to calculate dilutionof the sample.

Marker compounds may also include enzyme substrates such asp-nitrophenyl phosphate, glucose-6-phosphate dehydrogenase, andD-lactate. The compound p-nitrophenylphosphate is a substrate foralkaline phosphatase and may be configured to generate a coloredp-nitrophenol reaction product.

It is noted that the microfluidic improvements to the rotor describedherein (e.g., inlets, wells, arcuate cavity reflectors, conduit,container puncture mechanism, container, diluent, reagent, and the like)is not limited by a manufacturing process of the rotor. For example, therotor may be ultrasonically welded and/or laser welded.

II. Systems

Fluid Analysis System

Described herein are fluid analysis systems that may include one or moreof the components necessary to perform fluid analysis using the devicesaccording to various embodiments described herein. For example, thefluid analysis systems described herein may automatically process andanalyze a sample applied to a rotor device to identify and/or analyzeone or more analytes. Generally, the fluid analysis systems describedherein may include one or more of a rotor assembly, a radiation source,a detector, and a controller (including memory, a processor, andcomputer instructions). The radiation source may be configured to emit alight signal (e.g., light beam) and to illuminate a set of wells of therotor. A detector may be configured to receive the light beam passedthrough the rotor. A controller coupled to the detector may beconfigured to receive signal data corresponding to the light beamreceived by the detector and generate analyte data using the signaldata. One or more analytes of the fluid may be identified by thecontroller using the analyte data. The sample may include at least oneor more of whole blood, serum, plasma, urine, sputum, semen, saliva,ocular lens fluid, cerebral fluid, spinal fluid, amniotic fluid, andtissue culture media, as well as food and industrial chemicals,combinations thereof, and the like.

Rotor Manufacturing System

Described herein are rotor manufacturing systems that may include one ormore of the components necessary to manufacture the rotor devicesdescribed herein. For example, the manufacturing systems describedherein may couple (e.g., attach, weld) one or more layers of a rotorassembly together. Generally, the manufacturing systems described hereinmay include one or more of a platform configured to hold one or morerotor components, a radiation source, a photomask, and a controller(including memory, a processor, and computer instructions). In someembodiments, the platform may be a “floating” platform configured tohold a rotor and provide precise alignment and coupling with a photomaskhoused in a photomask housing. The radiation source may be configured toemit a light signal (e.g., light beam) for laser welding one or morelayers of a rotor assembly together. Any of the rotor devices (100, 200,300, 400, 500, 600, 700) as described herein may be manufactured usingthe rotor manufacturing systems as described herein.

Platform

In some embodiments, a photomask may be aligned to a platform configuredto hold a rotor for laser welding. Due to the size of microfluidicchannels, the photomask and rotor need to be aligned precisely in orderto properly laser weld a rotor using a photomask. To ensure consistentand proper alignment between the photomask and each rotor part to bewelded, a platform may be configured to move in a plane parallel to thephotomask to aid alignment of the rotor to the photomask. For example, aphotomask may be held at a fixed position and the rotor base may be heldon a platform (e.g., nest, stage) that may “float” relative to thephotomask to aid positioning and clamping of the photomask to the rotor.

FIG. 16 is a perspective view of a platform (1600) (e.g., “floatingplatform”) that may include a weld nest (1610) having a first set ofprotrusions (1620) and a second set of protrusions (1630) disposedthereon on a side facing a photomask housing (see FIG. 18). The firstset of protrusions (1620) (e.g., guide pins) may be configured to bereceived in corresponding holes in a photomask housing. The second setof protrusions (1630) (e.g., rotor alignment pins) may be configured tobe received in corresponding holes (e.g., recesses) in a rotor (1600)such that the rotor is held on the platform (1600). The first and secondset of protrusions may each include at least two protrusions. Theplatform may further include one or more alignment mechanisms (1640)(e.g., adjustment screws) that may be configured to move the weld nest(1610) along a plane of the platform (1600), thereby allowing the firstset of protrusions (1620) to mate with a photomask coupling. Thealignment mechanism (1640) may be manually operated or automaticallycontrolled by an actuation mechanism (e.g., operated by a controldevice).

FIG. 17 is an exploded perspective view of a photomask housing (1700)including a first layer (1710) (e.g., first housing), a second layer(1720) (e.g., glass plate), a photomask (1730), and a third layer (1740)(e.g., second housing). The first layer (1710) may include a set ofbushings (1750) (e.g., guide bushings) corresponding to the first set ofprotrusions (1620) of the platform (1600). In some embodiments, thephotomask housing (1700) may be fixed relative to the platform (1600).In this configuration, the floating platform allows the bushings andprotrusions (e.g., bushing guide pins, rotor alignment pins) to moverelative to each other and to fit into each other such that thephotomask may be releasably clamped to the rotor. FIG. 18 illustrates arotor (1800) held on the platform (1600) and in position to be advancedtoward and releasably clamped to the photomask housing (1700). Theplatform (1600) may be actuated along an axis perpendicular to thephotomask housing (1700). In some embodiments, the photomask may beconfigured to block infrared radiation to one or more portions of therotor coupled to the platform.

Rotor Inspection System

Described herein are rotor inspection systems that may include one ormore of the components necessary to perform weld analysis of rotordevices according to various embodiments described herein. For example,the inspection systems described herein may optically image, process,and analyze a rotor to generate rotor data corresponding to one or morestructures/structural features of the rotor. For example, the rotor datamay correspond to one or more of a set of welds, structures (e.g.,cavities, channels, wells), and reagents of the rotor. Generally, theinspection systems described herein may include one or more of aradiation source (e.g., illumination source), a detector, and acontroller (including memory, a processor, and computer instructions).The radiation source may be configured to emit a light signal (e.g.,light beam) and to illuminate one or more structures of the rotor. Adetector may be configured to receive the light beam reflected by therotor. A controller coupled to the detector may be configured to receivesignal data corresponding to the light beam received by the detector andgenerate rotor data using the signal data. One or more structures of therotor may be identified and characterized using the rotor data. Forexample, a rotor exceeding a predetermined number of low-quality weldsmay be marked as rejected by the rotor inspection system. As anotherexample, a rotor having a predetermined number of broken lyophilizedreagent spheres may be flagged for manual inspection. Any of the rotordevices (100, 200, 300, 400, 500, 600, 700) as described herein may beinspected using the rotor inspection systems as described herein.

Rotor Assembly

Any of the centrifugal rotors (100, 200, 300, 400, 500, 600, 700) asdescribed herein may be used with the fluid analysis systems asdescribed herein. In some embodiments, a rotor may include a fourthlayer to aid in handling, processing, and identification of a sampleapplied to the rotor. The fourth layer holding the rotor may be placedby a user into a fluid analysis system for automated processing of thesample. The fourth layer may be useful in providing physical support andprotection to the rotor. For example, the fourth layer may form a sealaround an opening of the rotor. In some embodiments, the rotor case mayinclude one or more identifiers such as a barcode, QR code, and one ormore fiducials (e.g., colored/opaque points, ruler, slits, landmarks,markers), combinations thereof, and the like.

Radiation Source

The fluid analysis systems as described herein may include a radiationsource configured to emit a first light signal (e.g., illumination)directed at the centrifugal rotor. The radiation source may beconfigured to generate the light beam in the UV, visible, and/or near-IRwavelengths. A detector as described herein may be configured to receivea second light beam from the centrifugal rotor. The second light signalmay be generated in response to the illumination of the microfluidicchannel using the first light signal. The second light signal may beused to generate analyte data for analysis. In some embodiments, theradiation source may include one or more of a light emitting diode,laser, microscope, optical sensor, lens, and flash lamp. For example,the radiation source may generate light that may be carried by fiberoptic cables or one or more LEDs may be configured to provideillumination. In another example, a fiberscope including a bundle offlexible optical fibers may be configured to receive and propagate lightfrom an external light source.

Detector

Generally, the fluid analysis systems described herein may include adetector used to receive light signals (e.g., light beams) that passthrough a sample within a well of a centrifugal rotor. The receivedlight may be used to generate signal data that may be processed by aprocessor and memory to generate analyte data. The detector may bedisposed on a side of the centrifugal rotor opposite that of a radiationsource such that the detector receives a light beam (e.g., second lightsignal) from the radiation source that has passed through one or morewells of the centrifugal rotor. The detector may further be configuredto image one or more identifiers (e.g., barcode) and identifiers of thecentrifugal rotor. In some embodiments, the detector may include one ormore of a lens, camera, and measurement optics. For example, thedetector may include an optical sensor (e.g., a charged coupled device(CCD) or complementary metal-oxide semiconductor (CMOS) optical sensor)and may be configured to generate an image signal that is transmitted toa display. For example, the detector may include a camera with an imagesensor (e.g., a CMOS or CCD array with or without a color filter arrayand associated processing circuitry).

Control Device

The fluid analysis systems, rotor manufacturing systems, and rotorinspection systems as described herein may couple to one or more controldevices (e.g., computer systems) and/or networks. FIG. 8B is a blockdiagram of the control device (820). The control device (820) mayinclude a controller (822) having a processor (824) and a memory (826).In some embodiments, the control device (820) may further include acommunication interface (830). The controller (822) may be coupled tothe communication interface (830) to permit a user to remotely controlthe control device (820), radiation source (810), centrifugal rotorassembly (812), detector (814), and any other component of the system(800). The communication interface (830) may include a network interface(832) configured to connect the control device (820) to another system(e.g., Internet, remote server, database) over a wired and/or wirelessnetwork. The communication interface (830) may further include a userinterface (834) configured to permit a user to directly control thecontrol device (820).

Controller

Generally, the fluid analysis systems described herein may include acentrifugal rotor and corresponding control device coupled to aradiation source and detector. In some embodiments, a detector may beconfigured to generate signal data. The signal data may be received by acontroller and used to generate analyte data corresponding to one ormore analytes of a sample. The control device may accordingly identifyand/or characterize one or more analytes of a sample. As described inmore detail herein, the controller (822) may be coupled to one or morenetworks using a network interface (832). The controller (822) mayinclude a processor (824) and memory (826) coupled to a communicationinterface (830) including a user interface (834). The controller (822)may automatically perform one or more steps of centrifugal rotoridentification, processing, image analysis, and analyte analysis, andthus improve one or more of specificity, sensitivity, and speed of fluidanalysis.

The controller (822) may include computer instructions for operationthereon to cause the processor (824) to perform one or more of the stepsdescribed herein. In some embodiments, the computer instructions may beconfigured to cause the processor to receive signal data from thedetector, generate analyte data using the signal data, and identify oneor more analytes of the fluid using the analyte data. In someembodiments, the computer instructions may be configured to cause thecontroller to set imaging data parameters. The computer instructions maybe configured to cause the controller to generate the analyte data.Signal data and analysis may be saved for each well of each centrifugalrotor.

A control device (820), as depicted in FIG. 8B, may include a controller(822) in communication with the fluid analysis system (800) (e.g.,radiation source (810), centrifugal rotor assembly (812), and detector(814)). The controller (822) may include one or more processors (824)and one or more machine-readable memories (826) in communication withthe one or more processors (824). The processor (824) may incorporatedata received from memory (826) and user input to control the system(800). The memory (826) may further store instructions to cause theprocessor (824) to execute modules, processes, and/or functionsassociated with the system (800). The controller (822) may be connectedto and control one or more of a radiation source (810), centrifugalrotor assembly (812), detector (814), communication interface (830), andthe like by wired and/or wireless communication channels.

The controller (822) may be implemented consistent with numerous generalpurpose or special purpose computing systems or configurations. Variousexample computing systems, environments, and/or configurations that maybe suitable for use with the systems and devices disclosed herein mayinclude, but are not limited to software or other components within orembodied on a server or server computing devices such asrouting/connectivity components, multiprocessor systems,microprocessor-based systems, distributed computing networks, personalcomputing devices, network appliances, portable (e.g., hand-held) orlaptop devices. Examples of portable computing devices includesmartphones, personal digital assistants (PDAs), cell phones, tabletPCs, wearable computers taking the form of smartwatches and the like,and portable or wearable augmented reality devices that interface withthe patient's environment through sensors and may use head-mounteddisplays for visualization, eye gaze tracking, and user input.

Processor

The processor (824) may be any suitable processing device configured torun and/or execute a set of instructions or code and may include one ormore data processors, image processors, graphics processing units,physics processing units, digital signal processors, and/or centralprocessing units. The processor (824) may be, for example, a generalpurpose processor, Field Programmable Gate Array (FPGA), an ApplicationSpecific Integrated Circuit (ASIC), combinations thereof, and the like.The processor (824) may be configured to run and/or execute applicationprocesses and/or other modules, processes and/or functions associatedwith the system and/or a network associated therewith. The underlyingdevice technologies may be provided in a variety of component typesincluding metal-oxide semiconductor field-effect transistor (MOSFET)technologies like complementary metal-oxide semiconductor (CMOS),bipolar technologies like emitter-coupled logic (ECL), polymertechnologies (e.g., silicon-conjugated polymer and metal-conjugatedpolymer-metal structures), mixed analog and digital, combinationsthereof, and the like.

Memory

In some embodiments, the memory (826) may include a database (not shown)and may be, for example, a random access memory (RAM), a memory buffer,a hard drive, an erasable programmable read-only memory (EPROM), anelectrically erasable read-only memory (EEPROM), a read-only memory(ROM), Flash memory, combinations thereof, and the like. As used herein,database refers to a data storage resource. The memory (826) may storeinstructions to cause the processor (824) to execute modules, processes,and/or functions associated with the control device (820), such ascalibration, indexing, centrifugal rotor signal processing, imageanalysis, analyte analysis, notification, communication, authentication,user settings, combinations thereof, and the like. In some embodiments,storage may be network-based and accessible for one or more authorizedusers. Network-based storage may be referred to as remote data storageor cloud data storage. Signal data and analysis stored in cloud datastorage (e.g., database) may be accessible to authorized users via anetwork, such as the Internet. In some embodiments, database (840) maybe a cloud-based FPGA.

Some embodiments described herein relate to a computer storage productwith a non-transitory computer-readable medium (also may be referred toas a non-transitory processor-readable medium) having instructions orcomputer code thereon for performing various computer-implementedoperations. The computer-readable medium (or processor-readable medium)is non-transitory in the sense that it does not include transitorypropagating signals per se (e.g., a propagating electromagnetic wavecarrying information on a transmission medium such as space or a cable).The media and computer code (also may be referred to as code oralgorithm) may be those designed and constructed for a specific purposeor purposes.

Examples of non-transitory computer-readable media include, but are notlimited to, magnetic storage media such as hard disks, floppy disks, andmagnetic tape; optical storage media such as Compact Disc/Digital VideoDiscs (CD/DVDs); Compact Disc-Read Only Memories (CD-ROMs); holographicdevices; magneto-optical storage media such as optical disks; solidstate storage devices such as a solid state drive (SSD) and a solidstate hybrid drive (SSHD); carrier wave signal processing modules; andhardware devices that are specially configured to store and executeprogram code, such as Application-Specific Integrated Circuits (ASICs),Programmable Logic Devices (PLDs), Read-Only Memory (ROM), andRandom-Access Memory (RAM) devices. Other embodiments described hereinrelate to a computer program product, which may include, for example,the instructions and/or computer code disclosed herein.

The systems, devices, and methods described herein may be performed bysoftware (executed on hardware), hardware, or a combination thereof.Hardware modules may include, for example, a general-purpose processor(or microprocessor or microcontroller), a field programmable gate array(FPGA), an application specific integrated circuit (ASIC), combinationsthereof, and the like. Software modules (executed on hardware) may beexpressed in a variety of software languages (e.g., computer code),including C, C++, Java®, Python, Ruby, Visual Basic®, and/or otherobject-oriented, procedural, or other programming language anddevelopment tools. Examples of computer code include, but are notlimited to, micro-code or micro-instructions, machine instructions, suchas produced by a compiler, code used to produce a web service, and filescontaining higher-level instructions that are executed by a computerusing an interpreter. Additional examples of computer code include, butare not limited to, control signals, encrypted code, and compressedcode.

Communication Interface

The communication interface (830) may permit a user to interact withand/or control the system (800) directly and/or remotely. For example, auser interface (834) of the system (800) may include an input device fora user to input commands and an output device for a user and/or otherusers (e.g., technicians) to receive output (e.g., view sample data on adisplay device) related to operation of the system (800). In someembodiments, a network interface (832) may permit the control device(820) to communicate with one or more of a network (870) (e.g.,Internet), remote server (850), and database (840) as described in moredetail herein.

User Interface

User interface (834) may serve as a communication interface between auser (e.g., operator) and the control device (820). In some embodiments,the user interface (834) may include an input device and output device(e.g., touch screen and display) and be configured to receive input dataand output data from one or more sensors, input device, output device,network (870), database (840), and server (850). For example, signaldata generated by a detector may be processed by processor (824) andmemory (826), and output visually by one or more output devices (e.g.,display). Signal data, image data, and/or analyte data may be receivedby user interface (834) and output visually, audibly, and/or throughhaptic feedback through one or more output devices. As another example,user control of an input device (e.g., joystick, keyboard, touch screen)may be received by user interface (834) and then processed by processor(824) and memory (826) for user interface (834) to output a controlsignal to one or more components of the fluid analysis system (800). Insome embodiments, the user interface (834) may function as both an inputand output device (e.g., a handheld controller configured to generate acontrol signal while also providing haptic feedback to a user).

Output Device

An output device of a user interface (834) may output image data and/oranalyte data corresponding to a sample and/or system (800), and mayinclude one or more of a display device, audio device, and hapticdevice. The display device may be configured to display a graphical userinterface (GUI). The user console (860) may include an integrateddisplay and/or video output that may be connected to output to one ormore generic displays, including remote displays accessible via theinternet or network. The output data may also be encrypted to ensureprivacy and all or portions of the output data may be saved to a serveror electronic healthcare record system. A display device may permit auser to view signal data, calibration data, functionalization data,image data, analyte data, system data, fluid data, patient data, and/orother data processed by the controller (822). In some embodiments, anoutput device may include a display device including at least one of alight emitting diode (LED), liquid crystal display (LCD),electroluminescent display (ELD), plasma display panel (PDP), thin filmtransistor (TFT), organic light emitting diodes (OLED), electronicpaper/e-ink display, laser display, holographic display, combinationsthereof, and the like.

An audio device may audibly output patient data, fluid data, image data,analyte data, system data, alarms and/or warnings. For example, theaudio device may output an audible warning when improper insertion ofthe centrifugal rotor into the centrifugal rotor assembly occurs. Insome embodiments, an audio device may include at least one of a speaker,piezoelectric audio device, magnetostrictive speaker, and/or digitalspeaker. In some embodiments, a user may communicate with other usersusing the audio device and a communication channel.

A haptic device may be incorporated into one or more of the input andoutput devices to provide additional sensory output (e.g., forcefeedback) to the user. For example, a haptic device may generate atactile response (e.g., vibration) to confirm user input to an inputdevice (e.g., joystick, keyboard, touch surface). In some embodiments,the haptic device may include a vibrational motor configured to providehaptic tactile feedback to a user. Haptic feedback may in someembodiments confirm initiation and completion of centrifugal rotorprocessing. Additionally or alternatively, haptic feedback may notify auser of an error such as improper placement and/or insertion of thecentrifugal rotor into a centrifugal rotor assembly. This may preventpotential harm to the system.

Input Device

Some embodiments of an input device may include at least one switchconfigured to generate a control signal. For example, the input devicemay be configured to control movement of the centrifugal rotor assembly.In some embodiments, the input device may include a wired and/orwireless transmitter configured to transmit a control signal to a wiredand/or wireless receiver of a controller (822). For example, an inputdevice may include a touch surface for a user to provide input (e.g.,finger contact to the touch surface) corresponding to a control signal.An input device including a touch surface may be configured to detectcontact and movement on the touch surface using any of a plurality oftouch sensitivity technologies including capacitive, resistive,infrared, optical imaging, dispersive signal, acoustic pulserecognition, and surface acoustic wave technologies. In embodiments ofan input device including at least one switch, a switch may include, forexample, at least one of a button (e.g., hard key, soft key), touchsurface, keyboard, analog stick (e.g., joystick), directional pad,pointing device (e.g., mouse), trackball, jog dial, step switch, rockerswitch, pointer device (e.g., stylus), motion sensor, image sensor, andmicrophone. A motion sensor may receive user movement data from anoptical sensor and classify a user gesture as a control signal. Amicrophone may receive audio and recognize a user voice as a controlsignal.

Network Interface

As depicted in FIG. 8A, a control device (820) described herein maycommunicate with one or more networks (870) and computer systems (850)through a network interface (832). In some embodiments, the controldevice (820) may be in communication with other devices via one or morewired and/or wireless networks. The network interface (832) mayfacilitate communication with other devices over one or more externalports (e.g., Universal Serial Bus (USB), multi-pin connector) configuredto couple directly to other devices or indirectly over a network (e.g.,the Internet, wireless LAN).

In some embodiments, the network interface (832) may include aradiofrequency receiver, transmitter, and/or optical (e.g., infrared)receiver and transmitter configured to communicate with one or moredevices and/or networks. The network interface (832) may communicate bywires and/or wirelessly with one or more of the sensors, user interface(834), network (870), database (840), and server (850).

In some embodiments, the network interface (832) may includeradiofrequency (RF) circuitry (e.g., RF transceiver) including one ormore of a receiver, transmitter, and/or optical (e.g., infrared)receiver and transmitter configured to communicate with one or moredevices and/or networks. RF circuitry may receive and transmit RFsignals (e.g., electromagnetic signals). The RF circuitry convertselectrical signals to/from electromagnetic signals and communicates withcommunications networks and other communications devices via theelectromagnetic signals. The RF circuitry may include one or more of anantenna system, an RF transceiver, one or more amplifiers, a tuner, oneor more oscillators, a digital signal processor, a CODEC chipset, asubscriber identity module (SIM) card, memory, and the like. A wirelessnetwork may refer to any type of digital network that is not connectedby cables of any kind.

Examples of wireless communication in a wireless network include, butare not limited to cellular, radio, satellite, and microwavecommunication. The wireless communication may use any of a plurality ofcommunications standards, protocols and technologies, including but notlimited to Global System for Mobile Communications (GSM), Enhanced DataGSM Environment (EDGE), high-speed downlink packet access (HSDPA),wideband code division multiple access (W-CDMA), code division multipleaccess (CDMA), time division multiple access (TDMA), Bluetooth,near-field communication (NFC), radio-frequency identification (RFID),Wireless Fidelity (Wi-Fi) (e.g., IEEE 802.11a, IEEE 802.11b, IEEE802.11g, IEEE 802.11n), Voice over Internet Protocol (VoIP), Wi-MAX, aprotocol for email (e.g., Internet Message Access Protocol (IMAP), PostOffice Protocol (POP)), instant messaging (e.g., eXtensible Messagingand Presence Protocol (XMPP), Session Initiation Protocol for InstantMessaging, Presence Leveraging Extensions (SIMPLE), Instant Messagingand Presence Service (IMPS)), Short Message Service (SMS), or any othersuitable communication protocol. Some wireless network deploymentscombine networks from multiple cellular networks or use a mix ofcellular, Wi-Fi, and satellite communication.

In some embodiments, a wireless network may connect to a wired networkin order to interface with the Internet, other carrier voice and datanetworks, business networks, and personal networks. A wired network istypically carried over copper twisted pair, coaxial cable, and/or fiberoptic cables. There are many different types of wired networks includingwide area networks (WAN), metropolitan area networks (MAN), local areanetworks (LAN), Internet area networks (IAN), campus area networks(CAN), global area networks (GAN), like the Internet, wireless personalarea networks (PAN) (e.g., Bluetooth, Bluetooth Low Energy), and virtualprivate networks (VPN). As used herein, network refers to anycombination of wireless, wired, public, and private data networks thatare typically interconnected through the Internet, to provide a unifiednetworking and information access system.

III. Methods

Described herein are embodiments corresponding to methods of using arotor for analyzing a fluid such as whole blood, manufacturing a rotor,and inspecting a rotor. These methods may identify and/or characterize asample and in some embodiments, may be used with the systems and devicesdescribed. For example, a fluid analysis system may analyze andcharacterize a blood sample placed on a rotor and identify one or moreanalytes. Generally, a biological sample may be input to a rotor, andthe rotor placed into a fluid analysis system. The system may then spinthe rotor by centrifugal force such that the sample is distributed intoa set of wells. The set of wells may be optically analyzed by the systemand further analysis may be performed to characterize the sample.

Some conventional rotors manufactured using ultrasonic weldingtechniques may generate reagent dust that may contribute to undesirablereagent contamination between cuvettes of the rotor. For example, whenportions of a rotor are ultrasonically welded, a reagent bead within acuvette may ultrasonically vibrate and generate reagent dust. In somecases, reagent dust may migrate out of a cuvette into a channel or othercavity of the rotor. By contrast, methods of manufacturing as describedherein may weld a plurality of rotor layers to form a rotor deviceaddress these deficiencies and that may be used with the fluid analysissystem. An inspection method may characterize one or more aspects of therotor and allow the rotor to be classified, such as based onmanufacturing quality.

Fluid Analysis

Methods for analyzing a fluid in some embodiments may use a fluidanalysis system and/or rotor as described herein. The methods describedherein may quickly and easily identify analytes from a sample based onoptical analysis techniques. FIG. 9 is a flowchart that generallyillustrates a method of analyzing a fluid (900). A rotor structurallyand/or functionally similar to the rotors (100, 200, 300, 400, 500, 600,700) as described herein may be used in one or more of the fluidanalysis steps described herein. The process may include, at step 902,applying a sample to a rotor. In some embodiments, the sample mayinclude a blood sample from a subject such as a human or animal. Forexample, the blood sample may be taken from a vein or from a fingerstick. A volume of the sample/fluid may be, for example, between about40 microliters and about 100 microliters. In some embodiments, the rotormay be packaged in an impermeable foil pouch, and may further include apackage of desiccant. Desiccant may minimize the impact of moisture on areagent disposed within the rotor. The sample may be input into a sampleport or opening of the rotor.

At step 904, the rotor having the sample may be placed (e.g., inserted)into a fluid analysis system. For example, the rotor may be configuredto be mounted on a centrifuge of the fluid analysis system (800). Therotor may include a receptacle or other coupling mechanism suitable formounting, for example, on a vertical drive shaft of the centrifuge. Forexample, the rotor may be placed onto a sliding platform configured toretract into the fluid analysis system and to allow a spindle (e.g.,shaft) to releasably engage with the rotor. In some embodiments, thespindle may engage a slidable diluent container within a cavity of therotor such that the container may be configured to open and directdiluent from the container into other cavities of the rotor for mixingwith the sample. For example, a container disposed within the rotor maybe pushed upward by a shaft towards a set of protrusions configured topuncture the container.

At step 906, the rotor may spin at one or more predetermined rates usingthe centrifuge. In embodiments where the sample includes blood, theblood cells may be separated from the diluted plasma by centrifugalforce at step 906. In other embodiments, separation of blood cells fromplasma may occur before dilution. In some embodiments, the sample maymix with the diluent to form a substantially homogenous mixture. Forexample, the rotor (100) illustrated in FIG. 1A may be spun at asuitable RPM such as, for example, at about 1,000 RPMs, at about 2,000RPMs, at about 3,000 RPMs, at about 4,000 RPMs, at about 5,000 RPMs, atabout 6,000 RPMs, including all values and sub-ranges in-between.

As the rotor spins, a sample may exit the arcuate cavity (110) whilediluent enters into metering chamber (112). The sample may begin to fillthe well (152) (e.g., red blood cell well) as the diluent flows from themetering chamber (112) to the mix chamber (114). The centrifugal forceof the spinning rotor prevents liquid from passing a U-shaped portion ofone or more conduits. When the rotor is at rest (e.g., not spinning),capillary forces allow the sample (e.g., plasma) to flow through one ormore conduits. One or more spin cycles may be used to deliver and mixthe sample and diluent in the mix chamber (114) as well deliver themixed diluent and sample into the channel (120) for distribution intothe set of wells (130).

After separation and mixing, at step 908, the sample fluid may bedistributed through the internal channels of the rotor into a set ofwells through centrifugal force. In some embodiments, the set of wellsmay include a set of assay wells, each well including one more reagents(e.g., lyophilized reagent, reagent beads), and a set of referencewells. Chemical reactions may occur between the fluid and reagent in theassay wells while plasma may enter the set of reference wells withoutundergoing a reaction with a reagent.

The fluid within the set of wells may be optically analyzed while therotor spins. For example, the chemical reactions occurring in the assaywells may be photometrically analyzed. At step 910, a radiation source(e.g., light source, illumination source) may be used to direct a lightbeam through one or more of the wells of the rotor. The radiation sourcemay include an arc lamp and/or other high intensity light sourceincluding a pulsed laser, wavelength tunable sources, combinationsthereof, and the like. For example, an arc lamp may dischargeapproximately 0.1 joules of energy during a flash of approximately 5microseconds in duration. The fluid within the set of wells maypartially absorb the light beam received from the radiation source. Thedegree to which the light is absorbed may depend on the wavelength ofthe light beam and the contents of the well being analyzed. In someembodiments, the radiation source may be activated based on a lightsignal received from a reflector of the rotor. For example, a reflectormay receive a light beam emitted in a plane of the rotor, which may beredirected perpendicularly toward a detector. The detector may receivethe light beam and a control device may process the signal data tocontrol the radiation source to emit a light beam at a predeterminedtime through a well of the rotor.

At step 912, a detector (e.g., optical sensor) may be used to receivethe light passed through one or more wells of the rotor. In someembodiments, the detector may be coupled to one or more opticalcomponents including one or more of a beam splitter, interferencefilter, and photodetector. The optical components may form an opticaldetection pathway (not shown). The detector at step 914 may beconfigured to generate signal data for one or more of the wells. At step916, the signal data may be processed by the control device tocharacterize (e.g., quantify) one or more analytes of the sample. Insome embodiments, a plurality of tests may be performed (e.g., up to 50different tests). For example, analysis may include an endpoint test anda rate test. Additionally or alternatively, immunoassays and otherspecific binding assays may be performed in the test wells. Generally,however, such assay procedures are homogeneous. In some cases,heterogeneous assay systems may be used when blood is separated fromplasma in the test wells after an immunological reaction step hasoccurred. Blood assays may include one or more of glucose, lactatedehydrogenase, serum glutamicoxaloacetic transaminase (SGOT), serumglutamic-pyruvic transaminase (SGPT), blood urea (nitrogen) (BUN), totalprotein, alkalinity, phosphatase, bilirubin, calcium, and chloride. Someof these assays may use blood plasma combined with one or more reagentsto generate a visually detectable (e.g., photometrically detectable)change in the plasma. At step 918, the analysis performed may be outputby the fluid analysis system.

Rotor Manufacturing

Also described herein are embodiments corresponding to methods formanufacturing a rotor that may be used in some embodiments with thefluid analysis system embodiments as described herein. A rotorstructurally and/or functionally similar to the rotors (100, 200, 300,400, 500, 600, 700) as described herein may be manufactured using one ormore of the manufacturing steps described herein. For example, themethods described here may manufacture a rotor device using injectionmolding and laser welding techniques. The rotors manufactured usingthese methods may have numerous benefits, such as rotors having areduced risk of reagent contamination (e.g., generation of bead dustwithin a well) as well as improvements to one or more of quality,consistency, throughput, and manufacturing automation.

Generally, the methods described herein include forming and bonding aset of layers of a rotor. For example, a base of the rotor may include afirst layer and a second layer that are bonded together such as througha two-shot injection molding process. The first layer may besubstantially transparent. The second layer may be substantiallyabsorbent to infrared radiation. The first layer and the second layermay define a set of wells. Furthermore, the second layer may define aset of channels and cavities as described in more detail herein. Therotor may include a third layer aligned to the base. The third layer maydefine an opening configured to receive a fluid where the third layermay be substantially transparent. The base may be bonded (e.g., welded)to the third layer using infrared radiation such that the channelestablishes a fluid communication path between the opening and the setof wells. In some embodiments, one or more additional layers may beformed and bonded to the third layer.

FIG. 10A is a flowchart that generally describes a method (1000) ofmanufacturing a rotor. The method may include, at step 1002, forming afirst layer and, at step 1004, forming a second layer. At step 1006, thefirst layer and the second layer may be bonded together to form a baseof the rotor. For example, the first layer and the second layer may beformed and bonded together (steps 1002, 1004, 1006) using multi-shotinjection molding (e.g., sequential injection molding) as described inmore detail with respect to FIGS. 10B and 11A-11F. In some embodiments,the first layer bonded to the second layer may define a set of wells.

In some embodiments, the first layer and the second layer may becomposed of one or more of acrylic, polycarbonate, cyclic olefincopolymers (COC), polystyrene, and acrylonitrile butadiene styrene(ABS). The first layer may be substantially transparent. For example,the first layer may be substantially transparent to at least one ofultraviolet light, visible light, and infrared radiation. The secondlayer may include at least about 0.1% by weight of carbon black. Forexample, the second layer may include about 0.2% of carbon black. Forexample, the second layer may include about 0.4% of carbon black. Forexample, the second layer may include about 0.8% of carbon black. Thesecond layer may be substantially absorbent to at least one ofmid-infrared radiation and near-infrared radiation. In some embodiments,the second layer may be substantially absorbent to at least 940 nmwavelength radiation.

In some embodiments, the first layer and the second layer of a rotor maybe formed and bonded using the two-shot molding process (1020) describedin the flowchart of FIG. 10B and illustrated in FIGS. 11A-11F. Asillustrated in FIG. 11B, a two-shot molding system/approach may includea first half of a mold (1120) and a corresponding second half of a mold(1130). The first half of a mold (1120) may include a first cavity(1122) and a second cavity (1124). The second half of a mold (1130) mayinclude a first core (1132) and a second core (1134). The shape of thefirst cavity (1122) and the second cavity (1124) may differ while theshape of the first core (1132) and the second core (1134) may be thesame. The different shapes between the first cavity (1122) and thesecond cavity (1124) allow different structures to be formed with eachinjection (e.g., shot) of material. Having the same shape between thefirst core (1132) and the second core (1134) allows the first layer tohave a consistent shape. The first half of a mold (1120) and the secondhalf of a mold (1130) may be formed of steel, for example. In someembodiments, either one of the first half of a mold (1120) and thesecond half of a mold (1130) may be configured to move axially androtate relative to the other. For example, the second half of a mold(1130) in FIGS. 11A-11F may be configured to move axially and rollrelative to a stationary first half of a mold (1120).

A two-shot molding process may include the step 1022 of closing a pairof mold halves (1120, 1130) and injecting (e.g., shooting) a firstmaterial (e.g., transparent resin material) into a first core (1132).The first layer of a first rotor (1140) will form between the molds(1120, 1130) and be defined by the shape of the first core (1132) andthe first cavity (1122).

At step 1024, the second half of a mold (1130) may move axially awayfrom the first half of a mold (1120) to open the mold. The first layerof the first rotor (1140) may be disposed within the first core (1132)of the second half of a mold (1130). At step 1026, the second half of amold (1130) may be rotated (e.g., rolled) 180 degrees such that thefirst cavity (1122) is aligned with the second core (1134) and thesecond cavity (1124) is aligned with the first core (1132) having thefirst layer of the first rotor (1140). This rotation of the second halfof a mold (1130) allows the first layer of the first rotor (1140) toreceive an injection of a second material (e.g., carbon-filled resinmaterial) over the first layer. That is, the second layer may be alignedwith the first layer. Concurrently, a first layer of a separate rotormay be injected in the adjacent second core (1134).

At step 1028, the pair of molds (1120, 1130) may be closed and a firstmaterial may be injected into the second core (1134). The first layer ofa second rotor (1142) may be formed between the molds (1120, 1130) andbe defined by the shape of the second core (1134) and the first cavity(1122). In parallel, a second material (e.g., carbon-filled resinmaterial) may be injected into the first core (1132). A second layer ofthe first rotor (1140) may be formed between the molds (1120, 1130) andbe defined by the shape of the first layer, the first core (1132), andthe second cavity (1124). That is, the second layer may be formed andbonded to the first layer using multi-shot injection molding.

As described in more detail herein, the second cavity (1124) and secondhalf of a mold (1130) may be configured to form a set of shut offs thatmay create a seal between the first and second materials and aidformation of structural features of a rotor (e.g., a set of wells). Forexample, a metal surface of the second cavity (1124) may engage with thefirst layer of a rotor to define a shut off configured to preventinjection of material and/or to create support. In particular, each wellof a set of wells may include a tapered sidewall surface (e.g., FIG. 3B)of a first layer that the second cavity (1124) may engage with to createa barrier configured to prevent the second material from flashing orbleeding. In this manner, one or more voids (e.g., wells) may be formedin the rotor.

At step 1030, the second half of a mold (1130) may move axially awayfrom the first half of a mold (1120) to open the mold. As shown in FIG.11E, the first layer of the second rotor (1142) may be disposed withinthe second core (1134) of the second half of a mold (1130). The firstrotor (1140) having the first layer and the second layer may be disposedwithin the second cavity (1124). At step 1032, the second half of a mold(1130) may be rotated (e.g., rolled) 180 degrees such that the firstcavity (1122) is aligned with the first core (1132) and the secondcavity (1124) is aligned with the second core (1134) having the firstlayer of the second rotor (1142). At step 1034, the first rotor (1140)having the first layer and the second layer bonded together (e.g., rotorbase) may be ejected from the second cavity (1124). The process mayreturn to step 1028 (e.g., FIG. 11D) for manufacturing additionalrotors. In other embodiments, second material (e.g., carbon-filledresin) may be shot before shooting the first material (e.g., transparentresin material).

Referring again to FIG. 10A, at step 1008, a set of lyophilized reagentsmay be placed into a set of the wells. For example, a first set of wellsmay be empty, a second set of wells may include different lyophilizedreagents, and each well of a third set of wells may include a pluralityof lyophilized reagents.

At step 1010, a third layer may be formed. For example, the third layermay be formed by injection molding. The third layer may be composed ofone or more of acrylic, polycarbonate, cyclic olefin copolymers (COC),polystyrene, and acrylonitrile butadiene styrene (ABS). The third layermay be substantially transparent. For example, the third layer may besubstantially transparent to at least one of ultraviolet light, visiblelight, and infrared radiation.

At step 1012, the first layer and the second layer may be bonded to thethird layer using infrared radiation such that a channel of the rotorestablishes a fluid communication path between the opening and the setof wells. For example, the first layer and the third layer may be laserwelded to the second layer. Laser welding may be performed using one ormore of a semiconductor diode laser, solid-state Nd:YAG laser, and fiberlaser. In some embodiments, a diode laser may generate a light beam witha wavelength of about 940 nm.

Step 1012 may include aligning the rotor base (e.g., first layer bondedto the second layer) to the third layer. In some embodiments, aphotomask may be aligned to the rotor base and the third layer. In someembodiments, the photomask may be held at a fixed position and the rotorbase may be held on a platform (e.g., nest, stage). For example, thephotomask may be clamped to the rotor base using the platform (e.g.,floating platform). The platform may be configured to move the rotorbase towards the photomask and align the photomask to the rotor base. Insome embodiments, the photomask may be configured to block infraredradiation to one or more portions of the rotor base and the third layer.Due to the precise tolerances needed between the rotor and photomask toensure proper welding, a platform may be configured to move in a planeparallel to the photomask to aid alignments of the rotor to thephotomask. A floating platform allows the bushings and protrusions(e.g., bushing guide pins, rotor alignment pins) to move relative toeach other and fit into each other such that the photomask may bereleasably clamped to the rotor. For example, as described in detailherein with respect to FIGS. 16-18, one of the photomask and platformmay include a set of bushings configured to fit into a corresponding setof protrusions of the other of the photomask and platform.

In some embodiments, the infrared radiation may be configured as a laserbeam. In some embodiments, the laser beam may be one or more of a linebeam, point-wise (e.g., spot) beam, field (e.g., planar) beam, and thelike. The laser beam may be output over the photomask, rotor base andthe third layer. For example, a line beam may be passed over thephotomask. The photomask may be configured to define a pattern of therotor weld. In portions of the rotor that receive the infrared radiationpassed through the photomask, a surface of the second layer may absorbthe infrared radiation and form a weld with a surface of the third layerin contact with the second layer. The line beam having a predeterminedwavelength (e.g., 940 nm) may be passed over the photomask to form alaser weld in the rotor in between about 1 second and about 2 seconds ata predetermined power output. In some portions of the rotor adjacent toa laser weld, a gap may be formed between about 1 μm and about 10 μmbetween the second layer and the third layer due to thermal expansion.

In some embodiments, the photomask may be configured to block the laserbeam over at least one lyophilized reagents of the set of lyophilizedreagents. This may aid structural and chemical integrity of a reagent.Additionally or alternatively, the laser beam may be output over atleast one other lyophilized reagent of the set of lyophilized reagents.Some of the lyophilized reagents disposed in the rotor may be configuredto receive infrared radiation at a predetermined wavelength, power, andtime while maintaining physical and chemical integrity of the reagent.For example, some reagents may function substantially identically to aphotomasked reagent when exposed to infrared radiation at about 940 nmfor between 1 second to about 2 seconds.

In other embodiments, the first layer and the second layer may be bondedusing one or more of ultrasonic welding, adhesives (e.g., adhesivetape), and/or solvent bonding.

At step 1014, a fourth layer may be formed. For example, the fourthlayer may be formed by injection molding. For example, a fourth layermay be structurally and/or functionally similar to the fourth layer(204, 704) as described herein. At step 1016, the fourth layer may becoupled to the third layer. For example, a fourth layer may beultrasonically welded to the third layer.

Rotor Inspection

Also described herein are embodiments corresponding to methods forinspecting a rotor that may be used in some embodiments with the fluidanalysis system embodiments as described herein. The methods describedhere may inspect a rotor device (e.g., laser welded rotor) using opticalimaging and analysis techniques. This may have numerous benefits, suchas quantifying one or more characteristics of a rotor. For example, oneor more rotor welds, reagent spheres, and wells may be analyzed andverified as part of a consistent, repeatable, and automated qualitycontrol process. This may be useful in categorizing a rotor such as byquality.

FIG. 12 is a flowchart that generally describes a method of inspecting arotor (1200). A rotor structurally and/or functionally similar to therotors (100, 200, 300, 400, 500, 600, 700) as described herein may beinspected using one or more of the inspection steps described herein.For example, the rotor may include a first layer (101, 201, 301, 501)coupled to a second layer (102, 202, 302, 402, 502, 702), such asthrough two-shot injection molding, to collectively define a set ofwells. The first layer may be substantially transparent. The secondlayer may define a channel. The second layer may be substantiallyabsorbent to infrared radiation. A third layer may define an openingconfigured to receive a fluid. The third layer may be substantiallytransparent and coupled to the second layer such as through laserwelding.

At step 1202, a rotor may be aligned to one or more optical sensors. Insome embodiments, one or more optical sensors may be configured togenerate a plan view, bottom view, skew view, and/or side view of therotor. In some embodiments, one or more radiation sources may beconfigured to illuminate the portions of the rotor to be imaged. Forexample, the rotor may be illuminated using diffuse axial illumination.In some embodiments, the rotor may be spinning while imaged.

At step 1204, a set of rotor images may be generated using one or moreof the optical sensors. For example, FIGS. 13A and 13B are illustrativeimages (1300, 1350) of portions of a rotor illustrating the structuralfeatures of the rotor from a plan view perspective. The images may be ofthe entire rotor or a portion of the rotor. In some embodiments, imagesmay be taken from any of a side and bottom perspective. At step 1206,one or more rotor characteristics may be identified from the set ofrotor images. Image analysis of the rotor images may be performed togenerate bonding information (e.g., data). In some embodiments, bondinginformation may include the results of a comparison performed betweenthe acquired image data and a set of reference data. The bondinginformation may include a set of edges formed between the second layerand the third layer. For example, an unexpected discontinuity in an edgemay indicate an incomplete weld. As shown in FIG. 13A, first portions(1310) of the rotor may have higher intensity values than secondportions (1320) of the rotor. For example, first portions (1310) of therotor may have a first pixel intensity range (e.g., 40-80 in a grayscalerange of 0-255) and second portions (1320) of the rotor may have asecond pixel intensity range (e.g., 100-140 in grayscale). Thedifference in contrast between the first portions (1310) and secondportions (1320) may be due to air within the second portions (1320). Thefirst portions (1310) may correspond to welded portions of the rotorwhile the second portions (1320) may correspond to unwelded portions ofthe rotor including one or more of the channels, wells, cavities,inlets, and manufacturing defects. Completely transparent rotors may notgenerate rotor images having such a visible contrast.

In FIG. 13B, first portions (1360) of the rotor have lower intensityvalues than second portions (1370, 1380) of the rotor. The firstportions (1360) may correspond to edges of a weld while the secondportions may correspond to structures of the rotor such as cavities(1370) and welded portions (1380). The bonding information may includeone or more gaps in the set of edges. For example, differences inintensity values between the acquired images (1300, 1350) and a set ofreference images for each location within the rotor may be used toidentify one or more gaps. Each of these differences may be identifiedas defects and included in the bonding information.

At step 1208, the rotor may be classified using the identified rotorcharacteristics. The number, size, shape, and location of the defectsmay be quantified and may be compared to a predetermined set ofthresholds. For example, some defects may have one or more of a sizebelow a predetermined threshold, location in an area that has minimalimpact on rotor integrity and/or functionality. Other defects may resultin categorization as one or more of rejected, restricted use (e.g.,approved for animal use but not human use), acceptable, limited release,requiring secondary inspection, manual inspection, and so forth. Thatis, there may a plurality of quality classifications. For example,incomplete welds that are isolated from a cavity, well, channel, inlet,and the like may be classified as cosmetic defects. In some cases, anincomplete weld that changes a shape of a channel, well, cavity, andinlet may be classified as a cosmetic or minor defect. In other cases,an incomplete weld that connects different structures together may beclassified as a critical defect. For example, an incomplete weld thatdirectly connects two conduits together or that directly connects twowells together may alter the microfluidic performance of the rotor suchthat the rotor may be classified as critically defective. In someembodiments, a combination of the number, size, shape, and location ofthe defects may be used to classify the rotor. High quality rotors arefree of incomplete welds that create new fluid flow paths betweendifferent chambers.

Additionally or alternatively, at step 1210, one or more reagentcharacteristics may be identified. For example, a set of reagent imagesmay be generated using one or more of the optical sensors. FIGS. 14A and14B are illustrative images (1400, 1450) of a well of a rotor having areagent. FIG. 14A is a side view of a well (1410) having two lyophilizedreagents (1420) disposed therein. FIG. 14B is a plan view of a well(1470) having at least one lyophilized reagent (1470) disposed therein.

Image analysis of the well images may be performed to generate reagentinformation (e.g., data). In some embodiments, reagent information mayinclude the results of a comparison performed between the acquired imagedata and a set of reference data. The reagent information may includecolor data and a set of edges defining a size and shape of the reagent.For example, the reagent information may be used to identify a reagentsphere broken up into multiple pieces and/or a lyophilized reagentsphere having one or more cleaved off portions.

At step 1212, the reagent may be classified using the reagentinformation. The number, size, shape, and location of the defects may bequantified and may be compared to a predetermined set of thresholds. Forexample, some defects may have one or more of a size and/or shapeoutside a predetermined boundary. The defects may result incategorization as one or more of rejected, acceptable, limited release,requiring secondary inspection, restricted use (e.g., approved foranimal use but not human use), cosmetic, manual inspection, and soforth. That is, there may a plurality of quality classifications. Insome embodiments, a combination of the number, size, shape, and locationof the defects may be used to classify the reagent and/or rotor.

At step 1214, the rotor and/or reagent analysis may be output by theinspection system. In some embodiments, a display may list the rotor andthe inspection result. Additionally or alternatively, a set of auditorytones (e.g., beeps) may be output to indicate a result of the rotorand/or reagent inspection. The analysis may also be stored in a remotedatabase as described herein.

As used herein, the terms “about” and/or “approximately” when used inconjunction with numerical values and/or ranges generally refer to thosenumerical values and/or ranges near to a recited numerical value and/orrange. In some instances, the terms “about” and “approximately” may meanwithin ±10% of the recited value. For example, in some instances, “about100 [units]” may mean within ±10% of 100 (e.g., from 90 to 110). Theterms “about” and “approximately” may be used interchangeably.

The foregoing description, for purposes of explanation, used specificnomenclature to provide a thorough understanding of various inventionsand embodiments disclosed herein. However, it will be apparent to oneskilled in the art that specific details are not required in order topractice the disclosed inventions and embodiments. Thus, the foregoingdescriptions of specific embodiments of the inventions and correspondingembodiments thereof are presented for purposes of illustration anddescription. They are not intended to be exhaustive or to limit theinvention to the precise forms disclosed; obviously, many modificationsand embodiments are possible in view of the above teachings. Theembodiments were chosen and described in order to best explain theprinciples of the inventions, the corresponding embodiments thereof, andpractical applications, so as to enable others skilled in the art tobest utilize the invention and various implementations with variousmodifications as are suited to the particular use contemplated. It isintended that the following claims and their equivalents define thescope of the invention.

In addition, any combination of two or more such features, structure,systems, articles, materials, kits, steps and/or methods, disclosedherein, if such features, structure, systems, articles, materials, kits,steps and/or methods are not mutually inconsistent, is included withinthe inventive scope of the present disclosure. Moreover, someembodiments of the various inventions disclosed herein may bedistinguishable from the prior art for specifically lacking one or morefeatures/elements/functionality found in a reference or combination ofreferences (i.e., claims directed to such embodiments may includenegative limitations).

Any and all references to publications or other documents, including butnot limited to, patents, patent applications, articles, webpages, books,etc., presented anywhere in the present application, are hereinincorporated by reference in their entirety. Moreover, all definitions,as defined and used herein, should be understood to control overdictionary definitions, definitions in documents incorporated byreference, and/or ordinary meanings of the defined terms.

The invention claimed is:
 1. A method for inspecting a microfluidicrotor, comprising: aligning a microfluidic rotor to an imaging device,the microfluidic rotor including a set of wells defined by a first layercoupled to a second layer, the first layer being substantiallytransparent to infrared radiation, the second layer defining a channel,the second layer being substantially absorbent to the infraredradiation, the microfluidic rotor further including a third layercoupled to the second layer and defining an opening configured toreceive a fluid, the third layer being substantially transparent to theinfrared radiation; generating a set of images of at least a portion ofthe microfluidic rotor using the imaging device; generating bondinginformation based on the set of images, the bonding informationincluding a set of edges and gaps formed between the second layer andthe third layer; and classifying a weld quality of the microfluidicrotor using the bonding information.
 2. The method of claim 1, whereinthe set of images includes one or more of a plan view of themicrofluidic rotor, a bottom view of the microfluidic rotor, a sideview, and a skew view of the microfluidic rotor.
 3. The method of claim1, the generating the set of images further includes illuminating themicrofluidic rotor.
 4. The method of claim 3, the illuminating themicrofluidic rotor includes employing diffuse axial illumination.
 5. Themethod of claim 1, the classifying the weld quality further includesidentifying one or more of a number, size, shape, and location of a setof defects in the microfluidic rotor.
 6. The method of claim 5, theclassifying the microfluidic rotor includes a set of rotorclassifications including one or more of rejected, acceptable, limitedrelease, and requiring secondary inspection.
 7. The method of claim 1,the aligning the microfluidic rotor includes orienting the imagingdevice parallel to the microfluidic rotor.
 8. The method of claim 1, thealigning the microfluidic rotor includes orienting the imaging deviceperpendicular to the microfluidic rotor.
 9. A method for inspecting amicrofluidic rotor, comprising: aligning a microfluidic rotor to animaging device, the microfluidic rotor including a set of wells definedby a first layer coupled to a second layer, the first layer beingsubstantially transparent to infrared radiation, and the second layerdefining a channel, the second layer being substantially absorbent tothe infrared radiation, and the microfluidic rotor further including athird layer coupled to the second layer and defining an openingconfigured to receive a fluid, the third layer being substantiallytransparent to the infrared radiation, wherein one or more wells of theset of wells includes a reagent; generating a set of reagent imagesusing the imaging device; generating reagent information from thereagent images, the reagent information including a shape and size ofthe reagent; and classifying a reagent quality using the reagentinformation.
 10. The method of claim 9, wherein the set of reagentimages includes one or more of a plan view of the reagent, a bottom viewof the reagent, and a side view of the reagent.
 11. The method of claim9, further comprising illuminating the reagent when generating thereagent images.
 12. The method of claim 11, the illuminating the reagentincludes employing diffuse axial illumination.
 13. The method of claim9, the classifying the reagent quality includes identifying one or moreof a number, size, shape, color, and location of the reagent in theapparatus.
 14. The method of claim 13, the classifying the reagentquality includes a set of rotor classifications including one or more ofrejected, acceptable, limited release, and requiring secondaryinspection.
 15. The method of claim 9, the aligning the apparatusincludes orienting the imaging device parallel to the apparatus.
 16. Themethod of claim 9, the aligning the apparatus includes orienting theimaging device perpendicular to the apparatus.
 17. The method of claim9, wherein the reagent is a lyophilized reagent.